BioMed Research International: Pharmaceutics The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Bioassay Directed Isolation and Biological Evaluation of Compounds Isolated from Rubus fairholmianus Gard. Mon, 01 Sep 2014 05:09:15 +0000 The in vitro and in silico analysis of Rubus fairholmianus acetone extract for antioxidant, antiproliferative, and anti-inflammatory activity led to the isolation of six compounds. Amongst all the six isolated compounds tested, 1-(2-hydroxyphenyl)-4-methylpentan-1-one (compound 1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (compound 2) were found to be more active in inhibiting BRCA and COX target proteins, which also showed the better results for DPPH and ABTS radical scavenging assays. The promising results of this investigation emphasize the importance of using R. fairholmianus in the treatment of radical generated disorders mainly cancer and other inflammatory diseases. Blassan Plackal George, Parimelazhagan Thangaraj, Cheruthazhakkatt Sulaiman, Shanmughavel Piramanayagam, and Sathish Kumar Ramaswamy Copyright © 2014 Blassan Plackal George et al. All rights reserved. Prospect of Stem Cell Conditioned Medium in Regenerative Medicine Thu, 28 Aug 2014 15:34:52 +0000 Background. Stem cell-derived conditioned medium has a promising prospect to be produced as pharmaceuticals for regenerative medicine. Objective. To investigate various methods to obtain stem cell-derived conditioned medium (CM) to get an insight into their prospect of application in various diseases. Methods. Systematic review using keywords “stem cell” and “conditioned medium” or “secretome” and “therapy.” Data concerning treated conditions/diseases, type of cell that was cultured, medium and supplements to culture the cells, culture condition, CM processing, growth factors and other secretions that were analyzed, method of application, and outcome were noted, grouped, tabulated, and analyzed. Results. Most of CM using studies showed good results. However, the various CM, even when they were derived from the same kind of cells, were produced by different condition, that is, from different passage, culture medium, and culture condition. The growth factor yields of the various types of cells were available in some studies, and the cell number that was needed to produce CM for one application could be computed. Conclusion. Various stem cell-derived conditioned media were tested on various diseases and mostly showed good results. However, standardized methods of production and validations of their use need to be conducted. Jeanne Adiwinata Pawitan Copyright © 2014 Jeanne Adiwinata Pawitan. All rights reserved. Niosomes of Ascorbic Acid and α-Tocopherol in the Cerebral Ischemia-Reperfusion Model in Male Rats Thu, 28 Aug 2014 08:41:24 +0000 The objective of the present study was to prepare a stable iv injectable formulation of ascorbic acid and α-tocopherol in preventing the cerebral ischemia. Different niosomal formulations were prepared by Span and Tween mixed with cholesterol. The physicochemical characteristics of niosomal formulations were evaluated in vitro. For in vivo evaluation, the rats were made ischemic by middle cerebral artery occlusion model for 30 min and the selected formulation was used for determining its neuroprotective effect against cerebral ischemia. Neuronal damage was evaluated by optical microscopy and transmission electron microscopy. The encapsulation efficiency of ascorbic acid was increased to more than 84% by remote loading method. The cholesterol content of the niosomes, the hydrophilicity potential of the encapsulated compounds, and the preparation method of niosomes were the main factors affecting the mean volume diameter of the prepared vesicles. High physical stability of the niosomes prepared from Span 40 and Span 60 was demonstrated due to negligible size change of vesicles during 6 months storage at 4–8°C. In vivo studies showed that ST60/Chol 35 : 35 : 30 niosomes had more neuroprotective effects against cerebral ischemic injuries in male rats than free ascorbic acid. Jaleh Varshosaz, Somayeh Taymouri, Abbas Pardakhty, Majid Asadi-Shekaari, and Abodolreza Babaee Copyright © 2014 Jaleh Varshosaz et al. All rights reserved. Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives Tue, 12 Aug 2014 09:00:00 +0000 The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field. Josune Torrecilla, Alicia Rodríguez-Gascón, María Ángeles Solinís, and Ana del Pozo-Rodríguez Copyright © 2014 Josune Torrecilla et al. All rights reserved. Impact of Seasons and Dioecy on Therapeutic Phytoconstituents of Tinospora cordifolia, a Rasayana Drug Sun, 10 Aug 2014 12:53:44 +0000 Tinospora cordifolia (Thunb.) Miers, Menispermaceae, is a dioecious creeper, commonly known as “Giloe” or “Guduchi” with significant medicinal importance in the traditional systems of medicine. It is designated as Rasayana drug in Ayurveda and recommended for a number of diseases and also as adaptogen and immunomodulator. The safety and efficacy of herbal medicines are closely correlated with the quality of the source materials. The aim of this study is to see the effect of seasons on phytoconstituents and how these vary in male and female stem samples of T. cordifolia. The study revealed that total phenolics and total sugar concentration obtained highest values in summer season while starch and tannin content were found maximum in winter season in both the genders. However, biomarkers, tinosporaside and berberine, reached to their highest concentration in monsoon season. Further, antioxidant potential revealed the highest inhibition percentage in winter season as well as in late summer season. The results of this study suggest that the female plant is best for its therapeutic phytoconstituents and the best harvesting seasons may be either winter or late summer for antioxidant potential and immunomodulator activities and monsoon for antidiabetic activity of T. cordifolia. Namrta Choudhry, Shweta Singh, Mohammad Badruzzaman Siddiqui, and Sayyada Khatoon Copyright © 2014 Namrta Choudhry et al. All rights reserved. The Influence of Ionizing Radiation, Temperature, and Light on Eplerenone in the Solid State Mon, 04 Aug 2014 06:35:36 +0000 Eplerenone was subjected to the influence of ionizing radiation in the form of a high-energy electron beam (25–400 kGy), high temperature (90°C RH 0% and 60°C RH 76.4%), and light (6 mln lux h). An HPLC method was used to determine the content of eplerenone and to establish the impurity profile of all samples. As eplerenone was found to be a compound of great resistance to the above stress factors with the exception of high doses of ionizing radiation (≥200 kGy) when its degradation was above 1%, it is possible to sterilize eplerenone by radiation method with the standard dose of 25 kGy. Based on the analysis of impurities and degradation products, the mechanism of radiodegradation was demonstrated to differ from the mechanisms of photo- and thermodegradation. The observation that the DSC curves for the nondegraded and degraded samples of eplerenone were significantly different only under exposure to the electron beam confirmed the applicability of DSC for studies of radiolytic degradation of eplerenone. Katarzyna Dettlaff, Magdalena Ogrodowczyk, Witold Kycler, Agnieszka Dołhań, Barbara Ćwiertnia, Piotr Garbacki, and Anna Jelińska Copyright © 2014 Katarzyna Dettlaff et al. All rights reserved. Investigations on Agglomeration and Haemocompatibility of Vitamin E TPGS Surface Modified Berberine Chloride Nanoparticles Mon, 04 Aug 2014 00:00:00 +0000 The objective of the present study is to investigate the influence of surface modification on systemic stability of NPs. Vitamin E TPGS (1% w/v) was used for surface modification of berberine chloride nanoparticles. Naked and surface modified NPs were incubated in different SBFs (pH 6.8 and 7.4) with or without bile salts and human plasma. NPs were observed for particle agglomeration and morphology by particle size analyzer and TEM, respectively. The haemocompatibility studies were conducted on developed NPs to evaluate their safety profile. The surface modified NPs were stable compared to naked NPs in different SBFs due to the steric stabilization property of vitamin E TPGS. Particle agglomeration was not seen when NPs were incubated in SBF (pH 6.8) with bile salts. No agglomeration was observed in NPs after their incubation in plasma but particle size of the naked NPs increased due to adhesion of plasma proteins. The TEM images confirmed the particle size results. DSC and FT-IR studies confirmed the coexistence of TPGS in surface modified NPs. The permissible haemolysis, LDH release, and platelet aggregation revealed that NPs were compatible for systemic administration. Thus, the study illustrated that the surface modification is helpful in the maintenance of stability of NPs in systemic conditions. Parameswara Rao Vuddanda, Vijayakumar Mahalingam Rajamanickam, Madhu Yaspal, and Sanjay Singh Copyright © 2014 Parameswara Rao Vuddanda et al. All rights reserved. Cytotoxicity Studies of Novel Combretastatin and Pterostilbene Derivatives Sun, 03 Aug 2014 08:27:01 +0000 We synthesised seven 2-aminestilbenes with methoxy substitents in reactions of dinitrostilbenes with sodium azide. In order to study the positioning of the nitro groups, the optimum structure of obtained stilbenes using the DFT B3LYP/6-311++G(2d,p) method was calculated. Very interesting aspect of this regioselectivity reaction is the fact that in all substrates and synthetized compounds the nitro groups in position 2 were not coplanar whereas the para-nitro groups were coplanar with respect to the benzene ring. Due to unique features of stilbene derivatives, such as antitumor agents, we undertook the studies on the biological properties of new stilbene derivatives. Using five cancer cell lines, we investigated the effects of 2-aminestilbenes with methoxy substitents on cell growth. Joanna Jakubowska, Justyna Mikuła-Pietrasik, Krzysztof Książek, and Hanna Krawczyk Copyright © 2014 Joanna Jakubowska et al. All rights reserved. Evaluation of the Influence of Formulation and Process Variables on Mechanical Properties of Oral Mucoadhesive Films Using Multivariate Data Analysis Wed, 23 Jul 2014 00:00:00 +0000 Oral mucosa is an attractive region for the local and systemic application of many drugs. Oral mucoadhesive films are preferred for their prolonged time of residence, the improved bioavailability of the drug they contain, their painless application, their protection against lesions, and their nonirritating properties. This work was focused on preparation of nonmedicated carmellose-based films using both solvent casting and impregnation methods, respectively. Moreover, a modern approach to evaluation of mucoadhesive films applying analysis of texture and subsequent multivariate data analysis was used. In this experiment, puncture strength strongly correlated with tensile strength and could be used to obtain necessary information about the mechanical film characteristics in films prepared using both methods. Puncture work and tensile work were not correlated in films prepared using the solvent casting method, as increasing the amount of glycerol led to an increase in the puncture work in thinner films. All measured texture parameters in films prepared by impregnation were significantly smaller compared to films prepared by solvent casting. Moreover, a relationship between the amount of glycerol and film thickness was observed, and a greater recalculated tensile/puncture strength was needed for an increased thickness in films prepared by impregnation. Hana Landová, David Vetchý, Jan Gajdziok, Petr Doležel, Jan Muselík, Kateřina Dvořáčková, Vladimír Jekl, Karel Hauptman, and Zdeněk Knotek Copyright © 2014 Hana Landová et al. All rights reserved. Assessment of Free Radical Scavenging Potential and Oxidative DNA Damage Preventive Activity of Trachyspermum ammi L. (Carom) and Foeniculum vulgare Mill. (Fennel) Seed Extracts Wed, 23 Jul 2014 00:00:00 +0000 Oxidation of biomolecules such as carbohydrates, proteins, lipids, and nucleic acids results in generation of free radicals in an organism which is the major cause of onset of various degenerative diseases. Antioxidants scavenge these free radicals, thereby protecting the cell from damage. The present study was designed to examine the free radical scavenging potential and oxidative DNA damage preventive activity of traditionally used spices Trachyspermum ammi L. (carom) and Foeniculum vulgare Mill. (fennel). The aqueous, methanolic, and acetonic extracts of T. ammi and F. vulgare seeds were prepared using soxhlet extraction assembly and subjected to qualitative and quantitative estimation of phytochemical constituents. Free radical scavenging potential was investigated using standard methods, namely, DPPH radical scavenging assay and ferric reducing antioxidant power assay along with the protection against oxidative DNA damage. The results stated that acetonic seed extracts (AAcSE and FAcSE) of both the spices possessed comparatively high amount of total phenolics whereas methanolic seed extracts (AMSE and FMSE) were found to have highest amount of total flavonoids. At 1 mg/mL concentration, highest DPPH radical scavenging activity was shown by FMSE (96.2%), AAcSE was recorded with highest FRAP value (2270.27 ± 0.005 μmol/L), and all the seed extracts have been shown to mitigate the damage induced by Fenton reaction on calf thymus DNA. Therefore, the study suggests that T. ammi and F. vulgare seed extracts could contribute as a highly significant bioresource of antioxidants to be used in our day-to-day life and in food and pharmaceutical industry. Nandini Goswami and Sreemoyee Chatterjee Copyright © 2014 Nandini Goswami and Sreemoyee Chatterjee. All rights reserved. Angiotensin I-Converting Enzyme Inhibitor Derived from Cross-Linked Oyster Protein Wed, 23 Jul 2014 00:00:00 +0000 Following cross-linking by microbial transglutaminase, modified oyster proteins were hydrolyzed to improve inhibitory activity against angiotensin-converting enzyme (ACE) inhibitory activity with the use of a single protease, or a combination of six proteases. The oyster hydrolysate with the lowest 50% ACE inhibitory concentration (IC50) of 0.40 mg/mL was obtained by two-step hydrolysis of the cross-linked oyster protein using Protamex and Neutrase. Five ACE inhibitory peptides were purified from the oyster hydrolysate using a multistep chromatographic procedure comprised of ion-exchange, size exclusion, and reversed-phase liquid chromatography. Their sequences were identified as TAY, VK, KY, FYN, and YA, using automated Edman degradation and mass spectrometry. These peptides were synthesized, and their IC50 values were measured to be 16.7, 29.0, 51.5, 68.2, and 93.9 μM, respectively. Toxicity of the peptides on the HepG2 cell line was not detected. The oyster hydrolysate also significantly decreased the systolic blood pressure of spontaneously hypertensive rats (SHR). The antihypertensive effect of the oyster hydrolysate on SHR was rapid and long-lasting, compared to commercially obtained sardine hydrolysate. These results suggest that the oyster hydrolysate could be a source of effective nutraceuticals against hypertension. Cheng-Liang Xie, Jin-Soo Kim, Jong-Myung Ha, Se-Young Choung, and Yeung-Joon Choi Copyright © 2014 Cheng-Liang Xie et al. All rights reserved. Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation Mon, 21 Jul 2014 08:28:22 +0000 Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72) and of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72) and higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension. Ritesh Fule and Purnima Amin Copyright © 2014 Ritesh Fule and Purnima Amin. All rights reserved. Hot-Stage Microscopy for Determination of API Particles in a Formulated Tablet Mon, 21 Jul 2014 00:00:00 +0000 Although methods exist to readily determine the particle size distribution (PSD) of an active pharmaceutical ingredient (API) before its formulation into a final product, the primary challenge is to develop a method to determine the PSD of APIs in a finished tablet. To address the limitations of existing PSD methods, we used hot-stage microscopy to observe tablet disintegration during temperature change and, thus, reveal the API particles in a tablet. Both mechanical and liquid disintegration were evaluated after we had identified optimum milling time for mechanical disintegration and optimum volume of water for liquid disintegration. In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs. Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness of our methodology. The availability of such a method equips pharmaceutical scientists with an in vitro assessment method that will more reliably determine the PSD of active substances in finished tablets. Michal Šimek, Veronika Grünwaldová, and Bohumil Kratochvíl Copyright © 2014 Michal Šimek et al. All rights reserved. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier Sun, 20 Jul 2014 09:33:07 +0000 Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. Ravi Kant Upadhyay Copyright © 2014 Ravi Kant Upadhyay. All rights reserved. UVA-UVB Photoprotective Activity of Topical Formulations Containing Morinda citrifolia Extract Tue, 15 Jul 2014 08:51:21 +0000 Exposure to solar radiation, particularly its ultraviolet (UV) component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formations, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. The beneficial photoprotective effects of topical formulations with the extract, Morinda citrifolia, have not been investigated. This present study aims to investigate the potential benefits of M. citrifolia topical application on the dorsal skin of mice, exposed to UVA-UVB light. Using 7 days of treatment, [before (baseline values) and 20 h after UV exposure], the thickness, skin barrier damage (TEWL), erythema, and histological alterations were evaluated. The results showed that the formulations containing the extract protected the skin against UV-induced damage. Mairim Russo Serafini, Cassia Britto Detoni, Paula dos Passos Menezes, Rose Nely Pereira Filho, Vanessa Silveira Fortes, Maria José Fonseca Vieira, Sílvia Stanisçuaski Guterres, Ricardo Luiz Cavalcanti de Albuquerque Junior, and Adriano Antunes de Souza Araújo Copyright © 2014 Mairim Russo Serafini et al. All rights reserved. Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation Mon, 14 Jul 2014 07:36:59 +0000 The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167–318 d·nm, PDI below 0.441, and −18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of with prolonged drug release of from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway. Deepak Sharma, Dipika Maheshwari, Gilphy Philip, Ravish Rana, Shanu Bhatia, Manisha Singh, Reema Gabrani, Sanjeev K. Sharma, Javed Ali, Rakesh Kumar Sharma, and Shweta Dang Copyright © 2014 Deepak Sharma et al. All rights reserved. Solid-Nanoemulsion Preconcentrate for Oral Delivery of Paclitaxel: Formulation Design, Biodistribution, and γ Scintigraphy Imaging Mon, 14 Jul 2014 00:00:00 +0000 Aim of present study was to develop a solid nanoemulsion preconcentrate of paclitaxel (PAC) using oil [propylene glycol monocaprylate/glycerol monooleate, 4 : 1 w/w], surfactant [polyoxyethylene 20 sorbitan monooleate/polyoxyl 15 hydroxystearate, 1 : 1 w/w], and cosurfactant [diethylene glycol monoethyl ether/polyethylene glycol 300, 1 : 1 w/w] to form stable nanocarrier. The prepared formulation was characterized for droplet size, polydispersity index, and zeta potential. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to assess surface morphology and drug encapsulation and its integrity. Cumulative drug release of prepared formulation through dialysis bag and permeability coefficient through everted gut sac were found to be remarkably higher than the pure drug suspension and commercial intravenous product (Intaxel), respectively. Solid nanoemulsion preconcentrate of PAC exhibited strong inhibitory effect on proliferation of MCF-7 cells in MTT assay. In vivo systemic exposure of prepared formulation through oral administration was comparable to that of Intaxel in γ scintigraphy imaging. Our findings suggest that the prepared solid nanoemulsion preconcentrate can be used as an effective oral solid dosage form to improve dissolution and bioavailability of PAC. Javed Ahmad, Showkat R. Mir, Kanchan Kohli, Krishna Chuttani, Anil K. Mishra, A. K. Panda, and Saima Amin Copyright © 2014 Javed Ahmad et al. All rights reserved. Antiulcerogenic Potential Activity of Free and Nanoencapsulated Passiflora serratodigitata L. Extracts Sun, 13 Jul 2014 11:20:50 +0000 This paper provides evidence that the leaves and stem of Passiflora serratodigitata L. dry crude extract (DCE), ethylacetate fraction (EAF), and residual water fraction show potential antiulcerogenic activity. Interestingly, the polymeric nanocapsule loaded with EAF had 10-fold more activity than the free EAF. Furthermore, the polymer nanoparticles provided homogeneous colloidal drug delivery systems and allowed overcoming challenges such as poor aqueous solubility as well as the physical-chemical instability of the organic extract, which presented 90% (w/w) of the flavonoid content. The entrapment efficiency of the total flavonoid was 90.6 ± 2.5% (w/v) for the DCE and 79.9 ± 2.7% (w/v) for the EAF. This study shows that nanoencapsulation improves both the physicochemical properties and the efficacy of the herbal formulations. Therefore, free and encapsulated extracts have the potential to be suitable drug design candidates for the therapeutic management of ulcer. Marc Strasser, Peky Noriega, Raimar Löbenberg, Nádia Bou-Chacra, and Elfriede M. Bacchi Copyright © 2014 Marc Strasser et al. All rights reserved. Exopolysaccharide from Ganoderma applanatum as a Promising Bioactive Compound with Cytostatic and Antibacterial Properties Thu, 10 Jul 2014 07:40:33 +0000 A new exopolysaccharide preparation isolated from stationary cultures of the white rot fungus Ganoderma applanatum (GpEPS) was tested in terms of its bioactive properties including its cytotoxic and immunostimulatory effect. The results indicate that the tested GpEPS (at concentrations above 22.85 µg/mL and 228.5 µg/mL) may exhibit selective activity against tumor cells (cell lines SiHa) and stimulate production of TNF-α THP-1-derived macrophages at the level of 752.17 pg/mL. The GpEPS showed antibacterial properties against Staphyloccoccus aureus and a toxic effect against Vibrio fischeri cells (82.8% cell damage). High cholesterol-binding capacity and triglycerides-binding capacity (57.9% and 41.6% after 24 h of incubation with the tested substances, resp.) were also detected for the investigated samples of GpEPS. Monika Osińska-Jaroszuk, Magdalena Jaszek, Magdalena Mizerska-Dudka, Adriana Błachowicz, Tomasz Piotr Rejczak, Grzegorz Janusz, Jerzy Wydrych, Jolanta Polak, Anna Jarosz-Wilkołazka, and Martyna Kandefer-Szerszeń Copyright © 2014 Monika Osińska-Jaroszuk et al. All rights reserved. Novel Resveratrol and 5-Fluorouracil Coencapsulated in PEGylated Nanoliposomes Improve Chemotherapeutic Efficacy of Combination against Head and Neck Squamous Cell Carcinoma Wed, 09 Jul 2014 00:00:00 +0000 Increasing consumption of tobacco and alcohol has led to a steady increase in the incidence of head and neck cancers in Asia. The drawbacks associated with the existing chemotherapeutic and surgical interventions have necessitated the development of a safer alternative for therapy of head and neck cancers. In this study we have explored the synergistic therapeutic potential of a phytochemical and chemotherapeutic agent using PEGylated liposomes as a delivery vehicle. Resveratrol and 5-fluorouracil were successfully coencapsulated in a single PEGylated nanoliposome. The thermal analysis and the nuclear magnetic resonance results revealed that resveratrol localized near the glycerol backbone of the liposomal membrane while 5-fluorouracil localized closer to the phosphate moiety, which influenced the release kinetics of both drugs. The nanoformulation was tested in vitro on a head and neck cancer cell line NT8e and was found to exhibit a GI50 similar to that of free 5-fluorouracil. Further, gene expression studies showed that the combination of resveratrol and 5-fluorouracil exhibited different effects on different genes that may influence the net antagonistic effect. The coencapsulation of resveratrol and 5-fluorouracil in a liposomal nanocarrier improved the cytotoxicity in comparison with the free drug combination when tested in vitro. Aarti Mohan, Shridhar Narayanan, Swaminathan Sethuraman, and Uma Maheswari Krishnan Copyright © 2014 Aarti Mohan et al. All rights reserved. Healing Efficacy of an EGF Impregnated Triple Gel Based Wound Dressing: In Vitro and In Vivo Studies Tue, 08 Jul 2014 00:00:00 +0000 To accomplish an ideal wound healing process which promotes healthy tissue growth with less scaring, a novel gel based topical drug delivery system composed of 3 different polymers chitosan, dextran sulfate, and polyvinylpyrrolidone K30 (CDP) was prepared. The physicochemical properties of the prepared gels were investigated in vitro. Gels showed a maximum swelling ratio of 50 ± 1.95 times of dried gel in PBS at pH 7.4. The swelling ratios increase in acidic and alkaline pH to 55.3 ± 1.75 and 65.5 ± 2.42, respectively. In the rheological test, prepared gels revealed viscoelastic properties and a small linear viscoelastic region of 0.166%. In vivo wound healing promoting activities of CDP gels containing 20 μg/mL EGF were evaluated on surgically induced dermal wounds in rats using pathologic examination. The application of CDP gel with incorporated EGF significantly reduced the defect on the rat’s skin and enhanced epithelial healing compared with the topical application of the EGF-free CDP gel. The results clearly substantiate the beneficial effects of the topical application of CDP containing EGF in the acceleration of healthy wound healing process with less scarring. Najmeh Khanbanha, Fatemeh Atyabi, Azade Taheri, Fatemeh Talaie, Mirgholamreza Mahbod, and Rassoul Dinarvand Copyright © 2014 Najmeh Khanbanha et al. All rights reserved. Curcumin Loaded Microsponges for Colon Targeting in Inflammatory Bowel Disease: Fabrication, Optimization, and In Vitro and Pharmacodynamic Evaluation Tue, 01 Jul 2014 10:38:27 +0000 The present study was aimed to develop and optimize the microsponges of curcumin for colon specific drug delivery in a view to bypass the upper gastrointestinal tract (GIT) for enhanced therapeutic effect. Microsponges were developed by quasi emulsion solvent diffusion method using 32 full factorial design. Prepared microsponges were optimized in order to analyze the effects of independent variables (volume of ethanol and Eudragit L100) on the encapsulation efficiency, particle size, and drug release. The optimized formulation was subjected to in vivo study using acetic acid induced colitis model in rats. The F7 was selected as optimized formulation based on particle size of 41.63 μm, % entrapment efficiency of 78.13%, and % cumulative drug release of 84.12%, and desirability factor of 0.83. Release studies revealed that microsponges prevented the premature release of curcumin in upper GIT and specifically released the drug at colonic pH. The drug release profile of F7 formulation was subjected to different kinetic models and based upon the best correlation coefficient () the release was found to follow Higuchi model, which suggested diffusion as the main mechanism of drug release. Pharmacodynamic study showed that curcumin loaded microsponges causes a significant decrease in edema, necrosis, and hemorrhage of colon as compared to free curcumin. This study proves that curcumin loaded microsponges may act as a promising drug delivery system for treatment of ulcerative colitis. Rashmi Sareen, Kavita Nath, Nitin Jain, and K. L. Dhar Copyright © 2014 Rashmi Sareen et al. All rights reserved. The Study of Naphthoquinones and Their Complexes with DNA by Using Raman Spectroscopy and Surface Enhanced Raman Spectroscopy: New Insight into Interactions of DNA with Plant Secondary Metabolites Sun, 22 Jun 2014 12:56:41 +0000 Naphthoquinones represent the group of plant secondary metabolites with cytotoxic properties based on their ability to generate reactive oxygen species and interfere with the processes of cell respiration. Due to this fact, the possible cytotoxic mechanisms on cellular and subcellular levels are investigated intensively. There are many targets of cytotoxic action on the cellular level; however, DNA is a critical target of many cytotoxic compounds. Due to the cytotoxic properties of naphthoquinones, it is necessary to study the processes of naphthoquinones, DNA interactions (1,4-naphthoquinone, binapthoquinone, juglone, lawsone, plumbagin), especially by using modern analytical techniques. In our work, the Raman spectroscopy was used to determine the possible binding sites of the naphthoquinones on the DNA and to characterize the bond of naphthoquinone to DNA. Experimental data reveals the relationships between the perturbations of structure-sensitive Raman bands and the types of the naphthoquinones involved. The modification of DNA by the studied naphthoquinones leads to the nonspecific interaction, which causes the transition of B-DNA into A-DNA conformation. The change of the B-conformation of DNA for all measured DNA modified by naphthoquinones except plumbagin is obvious. Veronika Vaverkova, Oldrich Vrana, Vojtech Adam, Tomas Pekarek, Josef Jampilek, and Petr Babula Copyright © 2014 Veronika Vaverkova et al. All rights reserved. Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/λ-Carrageenan Complexes Thu, 19 Jun 2014 10:06:17 +0000 In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer. Ruggero Bettini, Maria Cristina Bonferoni, Paolo Colombo, Laura Zanelotti, and Carla Caramella Copyright © 2014 Ruggero Bettini et al. All rights reserved. Increased Release Time of Antibiotics from Bone Allografts through a Novel Biodegradable Coating Thu, 19 Jun 2014 06:55:57 +0000 The use of bone allografts is contraindicated in septic revision surgery due to the high risk of graft reinfection. Antibiotic release from the graft may solve the problem and these combinations can theoretically be used for prevention or even therapy of infection. The present study investigated whether amoxicillin, ciprofloxacin, and vancomycin alone or in combination with chitosan or alginate are suitable for short-term or long-term bone coating. Human bone allografts were prepared from femoral head and lyophilized. Antibiotic coating was achieved by incubating the grafts in antibiotic solution and freeze-drying again. Two biopolymers chitosan and alginate were used for creating sustained-release implantable coatings and the drug release profile was characterized in vitro by spectrophotometry. Using lyophilization with or without chitosan only resulted in short-term release that lasted up to 48 hours. Alginate coating enabled a sustained release that lasted for 8 days with amoxicillin, 28 days with ciprofloxacin coating, and 50 days with vancomycin coating. Using only implantable biodegradable allograft and polymers, a sustained release of antibiotics was achieved with ciprofloxacin and vancomycin for several weeks. Since the calculated daily release of the antibiotic was lower than the recommended IV dose, the calcium alginate coated bone graft can support endoprosthesis revision surgery. István Hornyák, Edit Madácsi, Pálma Kalugyer, Gabriella Vácz, Dénes B. Horváthy, Miklós Szendrői, Weiping Han, and Zsombor Lacza Copyright © 2014 István Hornyák et al. All rights reserved. Topical Delivery of Aceclofenac: Challenges and Promises of Novel Drug Delivery Systems Wed, 18 Jun 2014 12:17:42 +0000 Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect about 60 million people of total world population by 2020. The associated pain and disability impair the quality of life and also pose economic burden to the patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in OA, while diclofenac is the most prescribed one. Oral NSAIDs are not very patient friendly, as they cause various gastrointestinal adverse effects like bleeding, ulceration, and perforation. To enhance the tolerability of diclofenac and decrease the common side effects, aceclofenac (ACE) was developed by its chemical modification. As expected, ACE is more well-tolerated than diclofenac and possesses superior efficacy but is not completely devoid of the NSAID-tagged side effects. A series of chemical modifications of already planned drug is unjustified as it consumes quanta of time, efforts, and money, and this approach will also pose stringent regulatory challenges. Therefore, it is justified to deliver ACE employing tools of drug delivery and nanotechnology to refine its safety profile. The present review highlights the constraints related to the topical delivery of ACE and the various attempts made so far for the safe and effective topical delivery employing the novel materials and methods. Kaisar Raza, Manish Kumar, Pramod Kumar, Ruchi Malik, Gajanand Sharma, Manmeet Kaur, and O. P. Katare Copyright © 2014 Kaisar Raza et al. All rights reserved. Formulation and Evaluation of Thermosensitive Biogels for Nose to Brain Delivery of Doxepin Wed, 18 Jun 2014 11:19:46 +0000 Thermoreversible biogels can serve as effective systems for delivery of drugs through nose with increased nasal residence time. The objective of this study was to use chitosan and glycerophosphate based thermoreversible systems for delivery of doxepin to brain through intranasal administration. Formulations were prepared by admixture of suitable dilutions of chitosan and glycerophosphate with or without polyethylene glycol, followed by addition of the antidepressant doxepin hydrochloride. Both systems were evaluated for gelling characteristics, rheology, mucoadhesion, in vitro release, and ex vivo permeation through sheep nasal mucosa. In vivo efficacy was evaluated in Swiss albino mice through the forced swim test. Nasal tissues of mice subjected to repeated exposure to formulation were evaluated histopathologically. Both formulations gelled rapidly at 37°C, returned to sol state on cooling, and exhibited thixotropy. Addition of polyethylene glycol decreased the glycerophosphate content required for gelation and rendered the formulation isotonic. Both gels showed good mucoadhesion, enhanced drug permeation, and provided prolonged in vitro release at 37°C. Efficacy of the formulation in treated groups was inferred from the measured pharmacodynamic parameter and histopathological reports of formulation treated groups showed no significant local toxicity. The biogels could be potential systems for effective drug delivery to brain via nose. Anuja Naik and Hema Nair Copyright © 2014 Anuja Naik and Hema Nair. All rights reserved. Formulation Optimization of Erythromycin Solid Lipid Nanocarrier Using Response Surface Methodology Wed, 18 Jun 2014 08:59:15 +0000 In present work response surface methodology (RSM) using the miscellaneous design model was used to optimize formulations of erythromycin solid lipid nanocarriers (ERY-SLN). Two-factor three level factorial design was considered for optimization. There were three parameters, drug entrapment efficiency (EE), drug loading (DL) percentage, and mean particle size of ERY-SLN, considered for investigating the optimal formulation with respect to two independent variables, including lipid concentration (X1) and surfactant : cosurfactant ratio (X2). The result showed that the optimal ERY-SLN was composed of lipid concentration (X1) 15 mg/mL and surfactant : cosurfactant ratio (X2) 1 : 1 with %EE of 88.40 ± 2.09%, DL of 29.46 ± 0.69%, mean particle size of 153.21 ± 2.31 nm, polydispersity index (PDI) of 0.026 ± 0.008, and zeta potential value of −15.18 ± (−5.53)  mV. DSC and TEM study showed that there was no chemical interaction between ERY and lipid (GMS) and the ERY-SLN particles are nonspherical, respectively. The drug release experiments exhibited a sustained release over during 24 h, up to 66.26 ± 2.83%. Accelerated stability studies showed that there was no significant change occurring in the responses after storage condition for a total period of 3 months. Anil Kumar Sahu, Tekeshwar Kumar, and Vishal Jain Copyright © 2014 Anil Kumar Sahu et al. All rights reserved. Growth Kinetics and Mechanistic Action of Reactive Oxygen Species Released by Silver Nanoparticles from Aspergillus niger on Escherichia coli Mon, 16 Jun 2014 09:19:40 +0000 Silver Nanoparticles (AgNPs), the real silver bullet, are known to have good antibacterial properties against pathogenic microorganisms. In the present study AgNPs were prepared from extracellular filtrate of Aspergillus niger. Characterization of AgNPs by UV-Vis spectrum reveals specific surface plasmon resonance at peak 416 nm; TEM photographs revealed the size of the AgNPs to be 20–55 nm. Average diameter of the produced AgNPs was found to be 73 nm with a zeta potential that was −24 mV using Malvern Zetasizer. SEM micrographs showed AgNPs to be spherical with smooth morphology. EDS revealed the presence of pure metallic AgNPs along with carbon and oxygen signatures. Of the different concentrations (0, 2.5, 5, 10, and 15 μg/mL) used 10 μg/mL were sufficient to inhibit 107 CFU/mL of E. coli. ROS production was measured using DCFH-DA method and the the free radical generation effect of AgNPs on bacterial growth inhibition was investigated by ESR spectroscopy. This paper not only deals with the damage inflicted on microorganisms by AgNPs but also induces cell death through the production of ROS released by AgNPs and also growth kinetics of E. coli supplemented with AgNPs produced by A. niger. Shivaraj Ninganagouda, Vandana Rathod, Dattu Singh, Jyoti Hiremath, Ashish Kumar Singh, Jasmine Mathew, and Manzoor ul-Haq Copyright © 2014 Shivaraj Ninganagouda et al. All rights reserved. In Vitro Ultrastructural Changes of MCF-7 for Metastasise Bone Cancer and Induction of Apoptosis via Mitochondrial Cytochrome C Released by CaCO3/Dox Nanocrystals Mon, 16 Jun 2014 07:25:01 +0000 Bones are the most frequent site for breast cancer cells to settle and spread (metastasise); bone metastasis is considered to have a substantial impact on the quality of patients with common cancers. However, majority of breast cancers develop insensitivity to conventional chemotherapy which provides only palliation and can induce systemic side effects. In this study we evaluated the effect of free Dox and CaCO3/Dox nanocrystal on MCF-7 breast cancer using MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide), neural red, and lactate dehydrogenase colorimetric assays while DNA fragmentation and BrdU genotoxicity were also examined. Apoptogenic protein Bax, cytochrome C, and caspase-3 protein were analysed. Morphological changes of MCF-7 were determined using contrast light microscope and scanning and transmission electron microscope (SEM and TEM). The findings of the analysis revealed higher toxicity of CaCO3/Dox nanocrystal and effective cells killing compared to free Dox, morphological changes such as formation of apoptotic bodies, membrane blebbing, and absent of microvilli as indicated by the SEM analysis while TEM revealed the presence of chromatin condensation, chromosomal DNA fragmentation, cell shrinkage, and nuclear fragmentation. Results of TUNEL assay verified that most of the cells undergoes apoptosis by internucleosomal fragmentation of genomic DNA whereas the extent of apoptotic cells was calculated using the apoptotic index (AI). Therefore, the biobased calcium carbonate nanocrystals such as Dox carriers may serve as an alternative to conventional delivery system. Abdullahi Shafiu Kamba, Maznah Ismail, Tengku Azmi Tengku Ibrahim, Zuki Abu Bakar Zakaria, and Lawal Hassan Gusau Copyright © 2014 Abdullahi Shafiu Kamba et al. All rights reserved. Neutralizing Effects of Mimosa tenuiflora Extracts against Inflammation Caused by Tityus serrulatus Scorpion Venom Wed, 11 Jun 2014 11:49:54 +0000 Scorpion bite represents a significant and serious public health problem in certain regions of Brazil, as well as in other parts of the world. Inflammatory mediators are thought to be involved in the systemic and local immune response induced by Tityus serrulatus scorpion envenomation. The aim of this study was to evaluate the effect of extracts of Mimosa tenuiflora on model envenomation. In mice, the envenomation model is induced by Tityus serrulatus venom. Previous treatment of mice with fractions from M. tenuiflora was able to suppress the cell migration to the peritoneal cavity. The treatment of mice with M. tenuiflora extracts also decreased the levels of IL-6, IL-12, and IL-1. We concluded that the administration of the extract and fractions resulted in a reduction in cell migration and showed a reduction in the level of proinflammatory cytokines. This study demonstrates, for the first time, the anti-inflammatory effect of aqueous extract from the Mimosa tenuiflora plant on T. serrulatus venom. Mariana Angélica Oliveira Bitencourt, Maira Conceição Jerônimo de Souza Lima, Manoela Torres-Rêgo, Júlia Morais Fernandes, Arnóbio Antônio da Silva-Júnior, Denise Vilarinho Tambourgi, Silvana Maria Zucolotto, and Matheus de Freitas Fernandes-Pedrosa Copyright © 2014 Mariana Angélica Oliveira Bitencourt et al. All rights reserved. Novel Lipid-Free Nanoformulation for Improving Oral Bioavailability of Coenzyme Q10 Thu, 05 Jun 2014 12:24:37 +0000 To improve the bioavailability of orally administered lipophilic coenzyme Q10 (CoQ10), we formulated a novel lipid-free nano-CoQ10 system stabilized by various surfactants. Nano-CoQ10s, composed of 2.5% (w/w) CoQ10, 1.67% (w/w) surfactant, and 41.67% (w/w) glycerol, were prepared by hot high-pressure homogenization. The resulting formulations were characterized by particle size, zeta potential, differential scanning calorimetry, and cryogenic transmission electron microscopy. We found that the mean particle size of all nano-CoQ10s ranged from  nm to  nm and the zeta potential ranged from  mV to  mV. The CoQ10 in nano-CoQ10s likely existed in a supercooled state, and nano-CoQ10s stored in a brown sealed bottle were stable for 180 days at 25°C. The bioavailability of CoQ10 was evaluated following oral administration of CoQ10 formulations in Sprague-Dawley rats. Compared to the values observed following administration of CoQ10-Suspension, nano-CoQ10 modified with various surfactants significantly increased the maximum plasma concentration and the area under the plasma concentration-time curve. Thus, the lipid-free system of a nano-CoQ10 stabilized with a surfactant may be an effective vehicle for improving oral bioavailability of CoQ10. Huafeng Zhou, Guoqing Liu, Jing Zhang, Ning Sun, Mingxing Duan, Zemin Yan, and Qiang Xia Copyright © 2014 Huafeng Zhou et al. All rights reserved. Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems Thu, 05 Jun 2014 09:56:16 +0000 Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed. Yulin Chen, Ping Ma, and Shuangying Gui Copyright © 2014 Yulin Chen et al. All rights reserved. Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom? Wed, 04 Jun 2014 09:03:40 +0000 Hallucinations are complex misperceptions, that principally occur in schizophrenia or after intoxication induced by three main classes of drugs: psychostimulants, psychedelics, and dissociative anesthetics. There are at least three different pharmacological ways to induce hallucinations: (1) activation of dopamine D2 receptors (D2Rs) with psychostimulants, (2) activation of serotonin 5HT2A receptors (HT2ARs) with psychedelics, and (3) blockage of glutamate NMDA receptors (NMDARs) with dissociative anesthetics. In schizophrenia, the relative importance of NMDAR and D2R in the occurrence of hallucinations is still debated. Slight clinical differences are observed for each etiology. Thus, we investigated whether the concept of hallucination is homogenous, both clinically and neurobiologically. A narrative review of the literature is proposed to synthesize how the main contributors in the field have approached and tried to solve these outstanding questions. While some authors prefer one explanatory mechanism, others have proposed more integrated theories based on the different pharmacological psychosis models. In this review, such theories are discussed and faced with the clinical data. In addition, the nosological aspects of hallucinations and psychosis are addressed. We suggest that if there may be common neurobiological pathways between the different pharmacological systems that are responsible for the hallucinations, there may also be unique properties of each system, which explains the clinical differences observed. Benjamin Rolland, Renaud Jardri, Ali Amad, Pierre Thomas, Olivier Cottencin, and Régis Bordet Copyright © 2014 Benjamin Rolland et al. All rights reserved. In Vitro Dissolution and In Vivo Bioavailability of Six Brands of Ciprofloxacin Tablets Administered in Rabbits and Their Pharmacokinetic Modeling Tue, 03 Jun 2014 12:01:45 +0000 This study was undertaken to assess the in vitro dissolution and in vivo bioavailability of six brands of ciprofloxacin oral tablets available in the UAE market using rabbits. The in vitro dissolution profiles of the six ciprofloxacin products were determined using the USP dissolution paddle method. Pharmacokinetic modeling using compartmental and noncompartmental analysis was done to determine the pharmacokinetic parameters of ciprofloxacin after single-dose oral administration. In vitro release study revealed that the amount of ciprofloxacin released in 20 minutes was not less than 80% of the labeled amount which is in accordance with the pharmacopoeial requirements. All tested products are considered to be very rapid dissolving except for formulae A and D. Ciprofloxacin plasma concentration in rabbits was best fitted to a two-compartment open model. The lowest bioavailability was determined to be for product A (93.24%) while the highest bioavailability was determined to be for product E (108.01%). Postmarketing surveillance is very crucial to ensure product quality and eliminating substandard products to be distributed and, consequently, ensure better patient clinical outcome. The tested ciprofloxacin generic products distributed in the UAE market were proven to be of good quality and could be used interchangeably with the branded ciprofloxacin product. Sahar Fahmy and Eman Abu-Gharbieh Copyright © 2014 Sahar Fahmy and Eman Abu-Gharbieh. All rights reserved. Solubility and Bioavailability Enhancement of Poorly Aqueous Soluble Atorvastatin: In Vitro, Ex Vivo, and In Vivo Studies Tue, 03 Jun 2014 11:28:50 +0000 The objective of this investigation was to improve the solubility of the poorly water soluble drug atorvastatin (ATR), using solid dispersion (SD) techniques, with Neem Gum (NG) as a hydrophilic carrier. The effects of the polymer concentration and method of preparation on the solubility and dissolution rate were studied. The results showed that the solubility of ATR increases with increasing NG concentration. However, dissolution rate of ATR from its SD was dependent on the method used to prepare SD. An in vitro drug release study revealed that the solvent evaporation technique is a more convenient and effective method of preparing SD than kneading method. The SD was characterized using DSC, SEM, and XRD study. An in vivo study was performed in which the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibition activity was measured. A significant reduction in HMG CoA reductase activity was observed with SD of ATR compared with the plain drug. An ex vivo absorption study was carried out using modified apparatus developed in our laboratory. The in vitro drug release and in vivo and ex vivo studies clearly demonstrated the potential of hydrophilic NG in enhancing the solubility, dissolution rate, and bioavailability of ATR. Madhuri S. Rodde, Ganesh T. Divase, Tejas B. Devkar, and Avinash R. Tekade Copyright © 2014 Madhuri S. Rodde et al. All rights reserved. Nonionic Surfactant Vesicles in Ocular Delivery: Innovative Approaches and Perspectives Tue, 03 Jun 2014 06:38:42 +0000 With the recent advancement in the field of ocular therapy, drug delivery approaches have been elevated to a new concept in terms of nonionic surfactant vesicles (NSVs), that is, the ability to deliver the therapeutic agent to a patient in a staggered profile. However the major drawbacks of the conventional drug delivery system like lacking of permeability through ocular barrier and poor bioavailability of water soluble drugs have been overcome by the emergence of NSVs. The drug loaded NSVs (DNSVs) can be fabricated by simple and cost-effective techniques with improved physical stability and enhance bioavailability without blurring the vision. The increasing research interest surrounding this delivery system has widened the areas of pharmaceutics in particular with many more subdisciplines expected to coexist in the near future. This review gives a comprehensive emphasis on NSVs considerations, formulation approaches, physicochemical properties, fabrication techniques, and therapeutic significances of NSVs in the field of ocular delivery and also addresses the future development of modified NSVs. Ranjan Ku. Sahoo, Nikhil Biswas, Arijit Guha, Nityananda Sahoo, and Ketousetuo Kuotsu Copyright © 2014 Ranjan Ku. Sahoo et al. All rights reserved. Experimental and Mathematical Studies on the Drug Release Properties of Aspirin Loaded Chitosan Nanoparticles Sun, 01 Jun 2014 00:00:00 +0000 The study of drug release dynamic is aiming at understanding the process that drugs release in human body and its dynamic characteristics. It is of great significance since these characteristics are closely related to the dose, dosage form, and effect of the drugs. The Noyes-Whitney function is used to represent how the solid material is dissolved into solution, and it is well used in study of drug dynamic. In this research, aspirin (acetylsalicylic acid (ASA)) has been encapsulated with different grades of chitosan (CS) varying in molecular weight (Mw) for the purpose of controlled release. The encapsulation was accomplished by ionic gelation technology based on assembly of positively charged chitosan and negatively charged sodium tripolyphosphate (TPP). The encapsulation efficiency, loading capacity, and drug release behavior of aspirin loaded chitosan nanoparticles (CS-NPs) were studied. It was found that the concentration of TPP and Aspirin, molecular weights of chitosan have important effect on the drug release patterns from chitosan nanoparticles. The results for simulation studies show that the Noyes-Whitney equation can be successfully used to interpret the drug release characteristics reflected by our experimental data. Yixiang Shi, Ajun Wan, Yifei Shi, Yueyue Zhang, and Yupeng Chen Copyright © 2014 Yixiang Shi et al. All rights reserved. Caffeic Acid Phenethyl Ester and Therapeutic Potentials Thu, 29 May 2014 13:12:20 +0000 Caffeic acid phenethyl ester (CAPE) is a bioactive compound of propolis extract. The literature search elaborates that CAPE possesses antimicrobial, antioxidant, anti-inflammatory, and cytotoxic properties. The principal objective of this review article is to sum up and critically assess the existing data about therapeutic effects of CAPE in different disorders. The findings elaborate that CAPE is a versatile therapeutically active polyphenol and an effective adjuvant of chemotherapy for enhancing therapeutic efficacy and diminishing chemotherapy-induced toxicities. Ghulam Murtaza, Sabiha Karim, Muhammad Rouf Akram, Shujaat Ali Khan, Saira Azhar, Amara Mumtaz, and Muhammad Hassham Hassan Bin Asad Copyright © 2014 Ghulam Murtaza et al. All rights reserved. Formulation of Indomethacin Colon Targeted Delivery Systems Using Polysaccharides as Carriers by Applying Liquisolid Technique Mon, 26 May 2014 07:15:06 +0000 The present study aimed at the formulation of matrix tablets for colon-specific drug delivery (CSDD) system of indomethacin (IDM) by applying liquisolid (LS) technique. A CSDD system based on time-dependent polymethacrylates and enzyme degradable polysaccharides was established. Eudragit RL 100 (E-RL 100) was employed as time-dependent polymer, whereas bacterial degradable polysaccharides were presented as LS systems loaded with the drug. Indomethacin-loaded LS systems were prepared using different polysaccharides, namely, guar gum (GG), pectin (PEC), and chitosan (CH), as carriers separately or in mixtures of different ratios of 1 : 3, 1 : 1, and 3 : 1. Liquisolid systems that displayed promising results concerning drug release rate in both pH 1.2 and pH 6.8 were compressed into tablets after the addition of the calculated amount of E-RL 100 and lubrication with magnesium stearate and talc in the ratio of 1 : 9. It was found that E-RL 100 improved the flowability and compressibility of all LS formulations. The release data revealed that all formulations succeeded to sustain drug release over a period of 24 hours. Stability study indicated that PEC-based LS system as well as its matrix tablets was stable over the period of storage (one year) and could provide a minimum shelf life of two years. Kadria A. Elkhodairy, Hanna A. Elsaghir, and Amal M. Al-Subayiel Copyright © 2014 Kadria A. Elkhodairy et al. All rights reserved. Stimuli-Sensitive Hydrogel Based on N-Isopropylacrylamide and Itaconic Acid for Entrapment and Controlled Release of Candida rugosa Lipase under Mild Conditions Sun, 25 May 2014 11:18:03 +0000 Stimuli responsive pH- and temperature-sensitive hydrogel drug delivery systems, as those based on N-isopropylacrylamide (NiPAAm) and itaconic acid (IA), have been attracting much of the attention of the scientific community nowadays, especially in the field of drug release. By adjusting comonomer composition, the matrix is enabled to protect the incorporated protein in the highly acidic environment of upper gastrointestinal tract and deliver it in the neutral or slightly basic region of the lower intestine. The protein/poly(NiPAAm-co-IA) hydrogels were synthetized by free radical crosslinking copolymerization and were characterized concerning their swelling capability, mechanical properties, and morphology. The pore structure and sizes up to 1.90 nm allowed good entrapment of lipase molecules. Model protein, lipase from Candida rugosa, was entrapped within hydrogels upon mild conditions that provided its protection from harmful environmental influences. The efficiency of the lipase entrapment reached 96.7%, and was dependent on the initial concentration of lipase solution. The swelling of the obtained hydrogels in simulated pH and temperature of gastrointestinal tract, the lipase entrapment efficiency, and its release profiles from hydrogels were investigated as well. Nikola Milašinović, Zorica Knežević-Jugović, Nedeljko Milosavljević, Marija Lučić Škorić, Jovanka Filipović, and Melina Kalagasidis Krušić Copyright © 2014 Nikola Milašinović et al. All rights reserved. Prediction on the Inhibition Ratio of Pyrrolidine Derivatives on Matrix Metalloproteinase Based on Gene Expression Programming Thu, 22 May 2014 12:10:34 +0000 Quantitative structure-activity relationships (QSAR) were developed to predict the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase via heuristic method (HM) and gene expression programming (GEP). The descriptors of 33 pyrrolidine derivatives were calculated by the software CODESSA, which can calculate quantum chemical, topological, geometrical, constitutional, and electrostatic descriptors. HM was also used for the preselection of 5 appropriate molecular descriptors. Linear and nonlinear QSAR models were developed based on the HM and GEP separately and two prediction models lead to a good correlation coefficient () of 0.93 and 0.94. The two QSAR models are useful in predicting the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase during the discovery of new anticancer drugs and providing theory information for studying the new drugs. Yuqin Li, Guirong You, Baoxiu Jia, Hongzong Si, and Xiaojun Yao Copyright © 2014 Yuqin Li et al. All rights reserved. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies Wed, 21 May 2014 07:11:26 +0000 Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C 2°C and % relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration () and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES). Praveen Kumar Gaur, Shikha Mishra, Meenakshi Bajpai, and Anushika Mishra Copyright © 2014 Praveen Kumar Gaur et al. All rights reserved. Application of Molecular Modeling to Urokinase Inhibitors Development Tue, 20 May 2014 07:05:33 +0000 Urokinase-type plasminogen activator (uPA) plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program), postprocessing (DISCORE program), direct generalized docking (FLM program), and the application of the quantum chemical calculations (MOPAC package), search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM. V. B. Sulimov, E. V. Katkova, I. V. Oferkin, A. V. Sulimov, A. N. Romanov, A. I. Roschin, I. B. Beloglazova, O. S. Plekhanova, V. A. Tkachuk, and V. A. Sadovnichiy Copyright © 2014 V. B. Sulimov et al. All rights reserved. Effect of Modulated Alternating and Direct Current Iontophoresis on Transdermal Delivery of Lidocaine Hydrochloride Thu, 15 May 2014 17:09:19 +0000 The objective of this study was to investigate the iontophoretic delivery of lidocaine hydrochloride through porcine skin and to compare the effects of modulated alternating and direct current iontophoresis. Continuous and modulated iontophoresis was applied for one hour and two hours (0-1 h and 4-5th h) using a 1% w/v solution of lidocaine hydrochloride. Tape stripping was done to quantify the amount of drug permeated into stratum corneum and skin extraction studies were performed to determine the amount of drug in stripped skin. Receptor was sampled and analyzed over predefined time periods. The amount of lidocaine delivered across porcine skin after modulated direct current iontophoresis for 2 h was  μg/sq·cm compared to  μg/sq·cm after modulated alternating current iontophoresis for 2 h. Modulated direct current iontophoresis also enhanced lidocaine delivery by twelvefold compared to passive delivery as  μg/sq·cm of lidocaine was delivered after passive delivery. Modulated iontophoresis enhanced the delivery of lidocaine hydrochloride across porcine skin compared to the passive delivery. Modulated alternating current iontophoresis for duration of 2 h at frequency of 1 kHz was found to be comparable to the continuous direct current iontophoresis for 1 h. Gaurav Bhatia and Ajay K. Banga Copyright © 2014 Gaurav Bhatia and Ajay K. Banga. All rights reserved. Implementation Study of Patient-Ready Syringes Containing 25 mg/mL Methotrexate Solution for Use in Treating Ectopic Pregnancy Mon, 12 May 2014 06:35:29 +0000 Background. Ectopic pregnancy (EP) is a significant cause of morbidity and mortality during the first trimester of pregnancy. Small unruptured tubal pregnancies can be treated medically with a single dose of methotrexate (MTX). Objective. The aim of this study was to evaluate the stability of a 25 mg/mL solution of MTX to devise a secure delivery circuit for the preparation and use of this medication in the management of EP. Method. MTX solutions were packaged in polypropylene syringes, stored over an 84-day period, and protected from light either at +2 to +8°C or at 23°C. We assessed the physical and chemical stability of the solutions at various time points over the storage period. A pharmaceutical delivery circuit was implemented that involved the batch preparation of MTX syringes. Results. We show that 25 mg/mL MTX solutions remain stable over an 84-day period under the storage conditions tested. Standard doses were prepared, ranging from 50 mg to 100 mg. The results of this study suggest that MTX syringes can be prepared in advance by the pharmacy, ready to be dispensed at any time that a diagnosis of EP is made. Conclusion. The high stability of a 25 mg/mL MTX solution in polypropylene syringes makes it possible to implement a flexible and cost-effective delivery circuit for ready-to-use preparations of this drug, providing 24-hour access and preventing treatment delays. R. Respaud, A. S. Gaudy, C. Arlicot, J. F. Tournamille, M. C. Viaud-Massuard, C. Elfakir, and D. Antier Copyright © 2014 R. Respaud et al. All rights reserved. Benchmarking B-Cell Epitope Prediction with Quantitative Dose-Response Data on Antipeptide Antibodies: Towards Novel Pharmaceutical Product Development Sun, 11 May 2014 11:37:52 +0000 B-cell epitope prediction can enable novel pharmaceutical product development. However, a mechanistically framed consensus has yet to emerge on benchmarking such prediction, thus presenting an opportunity to establish standards of practice that circumvent epistemic inconsistencies of casting the epitope prediction task as a binary-classification problem. As an alternative to conventional dichotomous qualitative benchmark data, quantitative dose-response data on antibody-mediated biological effects are more meaningful from an information-theoretic perspective in the sense that such effects may be expressed as probabilities (e.g., of functional inhibition by antibody) for which the Shannon information entropy (SIE) can be evaluated as a measure of informativeness. Accordingly, half-maximal biological effects (e.g., at median inhibitory concentrations of antibody) correspond to maximally informative data while undetectable and maximal biological effects correspond to minimally informative data. This applies to benchmarking B-cell epitope prediction for the design of peptide-based immunogens that elicit antipeptide antibodies with functionally relevant cross-reactivity. Presently, the Immune Epitope Database (IEDB) contains relatively few quantitative dose-response data on such cross-reactivity. Only a small fraction of these IEDB data is maximally informative, and many more of them are minimally informative (i.e., with zero SIE). Nevertheless, the numerous qualitative data in IEDB suggest how to overcome the paucity of informative benchmark data. Salvador Eugenio C. Caoili Copyright © 2014 Salvador Eugenio C. Caoili. All rights reserved. Evaluation of the DDSolver Software Applications Sun, 27 Apr 2014 00:00:00 +0000 When a new oral dosage form is developed, its dissolution behavior must be quantitatively analyzed. Dissolution analysis involves a comparison of the dissolution profiles and the application of mathematical models to describe the drug release pattern. This report aims to assess the application of the DDSolver, an Excel add-in software package, which is designed to analyze data obtained from dissolution experiments. The data used in this report were chosen from two dissolution studies. The results of the DDSolver analysis were compared with those obtained using an Excel worksheet. The comparisons among three different products obtained similarity factors of 23.21, 46.66, and 17.91 using both DDSolver and the Excel worksheet. The results differed when DDSolver and Excel were used to calculate the release exponent “” in the Korsmeyer-Peppas model. Performing routine quantitative analysis proved to be much easier using the DDSolver program than an Excel spreadsheet. The use of the DDSolver program reduced the calculation time and has the potential to omit calculation errors, thus making this software package a convenient tool for dissolution comparison. Jieyu Zuo, Yuan Gao, Nadia Bou-Chacra, and Raimar Löbenberg Copyright © 2014 Jieyu Zuo et al. All rights reserved. Libidibia ferrea Mature Seeds Promote Antinociceptive Effect by Peripheral and Central Pathway: Possible Involvement of Opioid and Cholinergic Receptors Tue, 22 Apr 2014 00:00:00 +0000 Libidibia ferrea (LF) is a medicinal plant that holds many pharmacological properties. We evaluated the antinociceptive effect in the LF aqueous seed extract and Lipidic Portion of Libidibia ferrea (LPLF), partially elucidating their mechanisms. Histochemical tests and Gas chromatography of the LPLF were performed to characterize its fatty acids. Acetic acid-induced abdominal constriction, formalin-induced pain, and hot-plate test in mice were employed in the study. In all experiments, aqueous extract or LPLF was administered systemically at the doses of 1, 5, and 10 mg/kg. LF aqueous seed extract and LPLF demonstrated a dose-dependent antinociceptive effect in all tests indicating both peripheral anti-inflammatory and central analgesia properties. Also, the use of atropine (5 mg/kg), naloxone (5 mg/kg) in the abdominal writhing test was able to reverse the antinociceptive effect of the LPLF, indicating that at least one of LF lipids components is responsible for the dose related antinociceptive action in chemical and thermal models of nociception in mice. Together, the present results suggested that Libidibia ferrea induced antinociceptive activity is possibly related to its ability to inhibit opioid, cholinergic receptors, and cyclooxygenase-2 pathway, since its main component, linoleic acid, has been demonstrated to produce such effect in previous studies. Luis Armando Sawada, Vanessa Sâmia da Conçeição Monteiro, Guilherme Rodrigues Rabelo, Germana Bueno Dias, Maura Da Cunha, José Luiz Martins do Nascimento, and Gilmara de Nazareth Tavares Bastos Copyright © 2014 Luis Armando Sawada et al. All rights reserved. Concomitant Intake of Quercetin with a Grain-Based Diet Acutely Lowers Postprandial Plasma Glucose and Lipid Concentrations in Pigs Wed, 16 Apr 2014 08:16:54 +0000 Treatment goals of diabetes mellitus type 2 (DMT2) include glycemic control and reduction of nonglycemic risk factors, for example, dyslipidemia. Quercetin, a plant-derived polyphenol, often discussed for possible antidiabetic effects, was investigated for acute postprandial glucose- and lipid-lowering effects in healthy growing pigs. Male pigs (, body weight = BW 25–30 kg) were fed flavonoid-poor grain-based meals without (GBM) or with quercetin (GBMQ). In a first experiment, postprandial plasma concentrations of glucose, nonesterified fatty acids (NEFA), and triacylglycerols were analyzed in 8 pigs receiving 500 g of either GBM or GBMQ (10 mg/kg BW) in a cross-over design. Blood samples were collected before, and up to 5 h every 30 min, as well as 6 and 8 h after the feeding. In the second experiment, 2 h after ingestions of 1000 g of either GBM or GBMQ (50 mg/kg BW) animals were sacrificed; gastric content was collected and analyzed for dry matter content. Quercetin ingestion reduced postprandial glucose, NEFA, and TG concentration, but two hours after ingestion of the meal no effect on gastric emptying was observed. Our results point to inhibitory effects of quercetin on nutrient absorption, which appear not to be attributable to delayed gastric emptying. Silvia Wein and Siegfried Wolffram Copyright © 2014 Silvia Wein and Siegfried Wolffram. All rights reserved. Recent Developments in Topical Wound Therapy: Impact of Antimicrobiological Changes and Rebalancing the Wound Milieu Tue, 15 Apr 2014 09:08:55 +0000 Wound therapy improves every year by developing new wound treatment options or by advancing already existing wound materials, for example, adding self-releasing analgesic drugs or growth factors to wound dressings, or by binding and inactivating excessive proteases. Also new dressing materials based on silk fibers and enhanced methods to reduce bacterial burden, for example, cold argon plasma, might help to fasten wound healing. Cornelia Erfurt-Berge and Regina Renner Copyright © 2014 Cornelia Erfurt-Berge and Regina Renner. All rights reserved. Assessment of Antioxidant Activity of Spray Dried Extracts of Psidium guajava Leaves by DPPH and Chemiluminescence Inhibition in Human Neutrophils Sun, 13 Apr 2014 15:55:31 +0000 This work evaluated the physicochemical properties and antioxidant activity of spray dried extracts (SDE) from Psidium guajava L. leaves. Different drying carriers, namely, maltodextrin, colloidal silicon dioxide, Arabic gum, and β-cyclodextrin at concentrations of 40 and 80% relative to solids content, were added to drying composition. SDE were characterized through determination of the total phenolic, tannins, and flavonoid content. Antioxidant potential of the SDE was assessed by two assays: cellular test that measures the luminol-enhanced chemiluminescence (LumCL) produced by neutrophils stimulated with phorbol myristate acetate (PMA) and the DPPH radical scavenging (DPPH* method). In both assays the antioxidant activity of the SDE occurred in a concentration-dependent manner and showed no toxicity to the cells. Using the CLlum method, the IC50 ranged from 5.42 to 6.50 µg/mL. The IC50 of the SDE ranged from 7.96 to 8.11 µg/mL using the DPPH• method. Psidium guajava SDE presented significant antioxidant activity; thus they show high potential as an active phytopharmaceutical ingredient. Our findings in human neutrophils are pharmacologically relevant since they indicate that P. guajava SDE is a potential antioxidant and anti-inflammatory agent in human cells. M. R. V. Fernandes, A. E. C. S. Azzolini, M. L. L. Martinez, C. R. F. Souza, Y. M. Lucisano-Valim, and W. P. Oliveira Copyright © 2014 M. R. V. Fernandes et al. All rights reserved. Development and Characterization of Liposomal Doxorubicin Hydrochloride with Palm Oil Thu, 27 Mar 2014 08:55:40 +0000 The usage of natural products in pharmaceuticals has steadily seen improvements over the last decade, and this study focuses on the utilization of palm oil in formulating liposomal doxorubicin (Dox). The liposomal form of Dox generally minimizes toxicity and enhances target delivery actions. Taking into account the antiproliferative and antioxidant properties of palm oil, the aim of this study is to design and characterize a new liposomal Dox by replacing phosphatidylcholine with 5% and 10% palm oil content. Liposomes were formed using the freeze_thaw method, and Dox was loaded through pH gradient technique and characterized through in vitro and ex vivo terms. Based on TEM images, large lamellar vesicles (LUV) were formed, with sizes of 438 and 453 nm, having polydispersity index of 0.21 ± 0.8 and 0.22 ± 1.3 and zeta potentials of about −31 and −32 mV, respectively. In both formulations, the entrapment efficiency was about 99%, and whole Dox was released through 96 hours in PBS (pH = 7.4) at 37°C. Comparing cytotoxicity and cellular uptake of LUV with on MCF7 and MDA-MBA 231 breast cancer cell lines indicated suitable uptake and lower IC50 of the prepared liposomes. Bahareh Sabeti, Mohamed Ibrahim Noordin, Shaharuddin Mohd, Rosnani Hashim, Afendi Dahlan, and Hamid Akbari Javar Copyright © 2014 Bahareh Sabeti et al. All rights reserved. Pegylated Gold Nanoparticles Induce Apoptosis in Human Chronic Myeloid Leukemia Cells Tue, 25 Mar 2014 14:49:34 +0000 Gold nanoparticles (AuNPs) have several potential biological applications as well as excellent biocompatibility. AuNPs with surface modification using polyethylene glycol (PEG-AuNPs) can facilitate easy conjugation with various biological molecules of interest. To examine the anticancer bioactivity of PEG-AuNPs, we investigated their effect on human chronic myeloid leukemia K562 cells. The results indicated that PEG-AuNPs markedly inhibited the viability and impaired the cell membrane integrity of K562 cells. The particles caused morphological changes typical of cell death, and a marked increase in the sub-G1 population in DNA histogram, indicating apoptosis. In addition, PEG-AuNPs reduced the mitochondrial transmembrane potential, a hallmark of the involvement of intrinsic apoptotic pathway in K562 cells. Observation of ultrastructure under a transmission electron microscope revealed that the internalized PEG-AuNPs were distributed into cytoplasmic vacuoles and damaged mitochondria, and subsequently accumulated in areas surrounding the nuclear membrane. In conclusion, PEG-AuNPs may have the potential to inhibit growth and induce apoptosis in human chronic myeloid leukemia cells. Yu-Chuen Huang, Yuh-Cheng Yang, Kai-Chien Yang, Hui-Ru Shieh, Tao-Yeuan Wang, Yeukuang Hwu, and Yu-Jen Chen Copyright © 2014 Yu-Chuen Huang et al. All rights reserved. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy Thu, 20 Mar 2014 08:46:26 +0000 Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy. Warangkana Lohcharoenkal, Liying Wang, Yi Charlie Chen, and Yon Rojanasakul Copyright © 2014 Warangkana Lohcharoenkal et al. All rights reserved. Topical Application of Retinyl Palmitate-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging Wed, 19 Mar 2014 12:47:20 +0000 The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS) with and without retinyl palmitate (RP). LCS containing polyether functional siloxane (PFS) as a surfactant, silicon glycol copolymer (SGC) as oil phase, and water in the ratios 30 : 25 : 45 and 40 : 50 : 10 with ( = RP-loaded opaque liquid system and = RP-loaded transparent liquid system, respectively) and without (OLS and TLS, respectively) RP were studied. Samples were characterized using polarized light microscopy (PLM) and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging. Marcela B. Oliveira, Alice Haddad do Prado, Jéssica Bernegossi, Claudia S. Sato, Iguatemy Lourenço Brunetti, Maria Virgínia Scarpa, Gislaine Ricci Leonardi, Stig E. Friberg, and Marlus Chorilli Copyright © 2014 Marcela B. Oliveira et al. All rights reserved. Film Coating of Nifedipine Extended Release Pellets in a Fluid Bed Coater with a Wurster Insert Tue, 18 Mar 2014 09:53:25 +0000 The objective of this work was to study the coating process of nifedipine extended release pellets using Opadry and Opadry II, in a fluid bed coater with a Wurster insert. The coating process was studied using a complete experimental design of two factors at two levels for each polymer. The variables studied were the inlet air temperature and the coating suspension flow rate. The agglomerate fraction and coating efficiency were the analyzed response variables. The air temperature was the variable that most influenced the coating efficiency for both polymers. In addition, a study of the dissolution profiles of coated and uncoated pellets using 0.5% sodium lauryl sulfate in simulated gastric fluid without enzymes (pH 1.2) was conducted. The results showed a prolonged release profile for the coated and uncoated pellets that was very similar to the standards established by the U.S. Pharmacopoeia. The drug content and the release profiles were not significantly affected by storage at 40°C and 75% relative humidity. However, when exposed to direct sunlight and fluorescent light (light from fluorescent bulbs), the coated pellets lost only 5% of the drug content, while the uncoated ones lost more than 35%; furthermore, the dissolution profile of the uncoated pellets was faster. Luciane Franquelin Gomes de Souza, Marcello Nitz, and Osvaldir Pereira Taranto Copyright © 2014 Luciane Franquelin Gomes de Souza et al. All rights reserved. Studies on the Antidiabetic Activities of Cordyceps militaris Extract in Diet-Streptozotocin-Induced Diabetic Sprague-Dawley Rats Tue, 11 Mar 2014 12:30:41 +0000 Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities of Cordyceps militaris on diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin, Cordyceps militaris extracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum. Cordyceps militaris extracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection of Cordyceps militaris extracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively, Cordyceps militaris extract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment. Yuan Dong, Tianjiao Jing, Qingfan Meng, Chungang Liu, Shuang Hu, Yihang Ma, Yan Liu, Jiahui Lu, Yingkun Cheng, Di Wang, and Lirong Teng Copyright © 2014 Yuan Dong et al. All rights reserved. Synthesis and Characterization of Folate-Targeted Dextran/Retinoic Acid Micelles for Doxorubicin Delivery in Acute Leukemia Sun, 02 Mar 2014 00:00:00 +0000 Folate and retinoic acid grafted/dextran (FA-RA/DEX) copolymers with different molecular weight of DEX were synthesized using carbonyldiimidazole and dimethylaminopyridine for targeted delivery of doxorubicin (DOX) in acute myelogenous leukemia (AML). The copolymers structure was confirmed by 1H NMR and FTIR. Critical micelle concentration (CMC) of each copolymer was determined using pyrene as a fluorescent probe. DOX was loaded in micelles by the direct dissolution method. Physical properties of micelles, including particle size, zeta potential, drug loading efficiency, and drug release profiles, were examined. The orientation of the folate ligand on the surface of the micelles was studied by X-ray photoelectron spectroscopy (XPS) technique. The cytotoxicity of micelles loaded with DOX at different concentrations was studied in KG1 cells using MTT assay and their cellular uptake by flow cytometry technique. FTIR and 1H NMR spectra confirmed successful production of the targeted micelles and XPS spectra showed the surface orientation of folate. R15D10F7 copolymer produced micelles with particle size of 82.86 nm, polydispersity index of 0.3, zeta potential of −4.68 mV, drug loading efficiency of 96%, and release efficiency of 63%. DOX loaded in folate-targeted micelles of RA/DEX was more toxic than that in nontargeted micelles and free drug and seems promising in reducing drug resistance in AML. J. Varshosaz, F. Hassanzadeh, H. Sadeghi Aliabadi, M. Nayebsadrian, M. Banitalebi, and M. Rostami Copyright © 2014 J. Varshosaz et al. All rights reserved. Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid) Bioadhesive Nanoparticles Thu, 20 Feb 2014 14:00:23 +0000 The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 g·kg−1), iv solution of sCT (5 g·kg−1), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly. J. Varshosaz, M. Minaiyan, and M. Forghanian Copyright © 2014 J. Varshosaz et al. All rights reserved. The Use of Hibiscus esculentus (Okra) Gum in Sustaining the Release of Propranolol Hydrochloride in a Solid Oral Dosage Form Tue, 11 Feb 2014 16:07:37 +0000 The effectiveness of Okra gum in sustaining the release of propranolol hydrochloride in a tablet was studied. Okra gum was extracted from the pods of Hibiscus esculentus using acetone as a drying agent. Dried Okra gum was made into powder form and its physical and chemical characteristics such as solubility, pH, moisture content, viscosity, morphology study using SEM, infrared study using FTIR, crystallinity study using XRD, and thermal study using DSC and TGA were carried out. The powder was used in the preparation of tablet using granulation and compression methods. Propranolol hydrochloride was used as a model drug and the activity of Okra gum as a binder was compared by preparing tablets using a synthetic and a semisynthetic binder which are hydroxylmethylpropyl cellulose (HPMC) and sodium alginate, respectively. Evaluation of drug release kinetics that was attained from dissolution studies showed that Okra gum retarded the release up to 24 hours and exhibited the longest release as compared to HPMC and sodium alginate. The tensile and crushing strength of tablets was also evaluated by conducting hardness and friability tests. Okra gum was observed to produce tablets with the highest hardness value and lowest friability. Hence, Okra gum was testified as an effective adjuvant to produce favourable sustained release tablets with strong tensile and crushing strength. Nurul Dhania Zaharuddin, Mohamed Ibrahim Noordin, and Ali Kadivar Copyright © 2014 Nurul Dhania Zaharuddin et al. All rights reserved. Uptake of Etoposide in CT-26 Cells of Colorectal Cancer Using Folate Targeted Dextran Stearate Polymeric Micelles Mon, 10 Feb 2014 00:00:00 +0000 Targeted drug delivery using folate receptors is one of the most interesting chemotherapeutic research areas over the past few years. A novel folate targeted copolymer was synthesized using dextran stearate coupled to folic acid. FT-IR and NMR spectroscopy were used to confirm successful conjugation. Micelles prepared using this copolymer were characterized for their particle size, zeta potential, critical micelle concentration (CMC), drug loading capacity, and release efficiency. Cytotoxicity and cellular uptake of the micelles were estimated using CT-26 colorectal carcinoma cell line. FT-IR and NMR spectroscopy confirmed production of folate grafted dextran stearate copolymer. Low CMC value indicates that the copolymers are suitable for preparation of stable micelles useful in parenteral dosage forms. Particle size and zeta potential of the targeted nanoparticles were  nm and −21.2 mV, respectively. IC50 of etoposide loaded in folate grafted dextran stearate enhanced about 20-fold compared to the pure drug ( μg/mL versus  μg/mL). It seems that etoposide loaded in micelles of folate grafted dextran stearate copolymer is promising in reducing drug resistance of colorectal cancer by boosting etoposide cellular uptake. Jaleh Varshosaz, Farshid Hassanzadeh, Hojjat Sadeghi-Aliabadi, and Farzin Firozian Copyright © 2014 Jaleh Varshosaz et al. All rights reserved. Induction of Apoptosis of 2,4′,6-Trihydroxybenzophenone in HT-29 Colon Carcinoma Cell Line Wed, 22 Jan 2014 11:57:58 +0000 2,4′,6-Trihydroxy-4-methoxybenzophenone was isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff.) Boerl. fruits. It was found to inhibit cell proliferation in HT-29 human colon carcinoma cell line but caused little damage to WRL-68 normal human liver and MRC-5 normal human fibroblast lung cell lines. The compound was found to sharply affect the viability of HT-29 cells in a dose- and time-dependent manner. HT-29 cells treated with the compound showed morphological changes under microscopic examination such as cell shrinkage, membrane blebbing, DNA fragmentation, and the occurrence of apoptotic nuclei. The percentage of early apoptotic, late apoptotic, and dead or necrotic cells was determined by flow cytometry using annexin V-FTIC/PI staining. In addition, flow cytometry showed that, when the HT-29 cells were treated with 115 µM of the compound, it resulted in G0/G1 phase arrest in a time-dependent manner. Western blot revealed an upregulation of PUMA, Bak, Bcl-2, and Mcl-1 proteins suggesting that the compound induced apoptosis in HT-29 cells by regulating these proteins. Ma Ma Lay, Saiful Anuar Karsani, and Sri Nurestri Abd Malek Copyright © 2014 Ma Ma Lay et al. All rights reserved. Carbon Nanotubes Hybrid Hydrogels in Drug Delivery: A Perspective Review Tue, 21 Jan 2014 08:59:45 +0000 The use of biologics, polymers, silicon materials, carbon materials, and metals has been proposed for the preparation of innovative drug delivery devices. One of the most promising materials in this field are the carbon-nanotubes composites and hybrid materials coupling the advantages of polymers (biocompatibility and biodegradability) with those of carbon nanotubes (cellular uptake, stability, electromagnatic, and magnetic behavior). The applicability of polymer-carbon nanotubes composites in drug delivery, with particular attention to the controlled release by composites hydrogel, is being extensively investigated in the present review. Giuseppe Cirillo, Silke Hampel, Umile Gianfranco Spizzirri, Ortensia Ilaria Parisi, Nevio Picci, and Francesca Iemma Copyright © 2014 Giuseppe Cirillo et al. All rights reserved. Soluplus Graft Copolymer: Potential Novel Carrier Polymer in Electrospinning of Nanofibrous Drug Delivery Systems for Wound Therapy Mon, 20 Jan 2014 08:01:35 +0000 Electrospinning is an effective method in preparing polymeric nanofibrous drug delivery systems (DDSs) for topical wound healing and skin burn therapy applications. The aim of the present study was to investigate a new synthetic graft copolymer (Soluplus) as a hydrophilic carrier polymer in electrospinning of nanofibrous DDSs. Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG)) was applied in the nonwoven nanomats loaded with piroxicam (PRX) as a poorly water-soluble drug. Raman spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy (SEM) were used in the physical characterization of nanofibrous DDSs. According to the SEM results, the drug-loaded PCL-PVAc-PEG nanofibers were circular in cross-section with an average diameter ranging from 500 nm up to 2 µm. Electrospinning stabilized the amorphous state of PRX. In addition, consistent and sustained-release profile was achieved with the present nanofibrous DDSs at the physiologically relevant temperature and pH applicable in wound healing therapy. In conclusion, electrospinning can be used to prepare nanofibrous DDSs of PCL-PVAc-PEG graft copolymer (Soluplus) and to stabilize the amorphous state of a poorly water-soluble PRX. The use of this synthetic graft copolymer can open new options to formulate nanofibrous DDSs for wound healing. Urve Paaver, Ingrid Tamm, Ivo Laidmäe, Andres Lust, Kalle Kirsimäe, Peep Veski, Karin Kogermann, and Jyrki Heinämäki Copyright © 2014 Urve Paaver et al. All rights reserved. Antiproliferative Activity of the Isofuranonaphthoquinone Isolated from Bulbine frutescens against Jurkat T Cells Thu, 16 Jan 2014 11:59:41 +0000 Cancer is a major public health burden in both developed and developing countries. The quinone moiety has been shown to possess antitumor activity and several cancer drugs in clinical use contain this entity. The effect of isofuranonaphthoquinone isolated from Bulbine frutescens on Jurkat T cells was determined. Cells were exposed to the isofuranonaphthoquinone (IFNQ) at different concentrations. Significant antiproliferative effects were observed which were comparable to that of the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). A combination of IFNQ with BCNU produced synergistic effects which were observed after 72 hrs. It was also observed that combining IFNQ with reduced glutathione abolished the anticancer activity of the compound. It is, therefore, proposed that the isofuranonaphthoquinone may exert part of its effect by producing reactive oxygen species resulting in death of the cells as the effects of this compound were antagonized by reduced glutathione. An investigation on the effects of isofuranonaphthoquinone on glutathione transferase (GST) activity and drug efflux pumps showed that this compound exhibited inhibitory effects on both the GST and the drug efflux pumping activities. Thus, the isofuranonaphthoquinone showed cytotoxicity, works through inhibition of some cellular mechanisms, and could present a potential source of lead compounds for anticancer drug development. Penelope Tambama, Berhanu Abegaz, and Stanley Mukanganyama Copyright © 2014 Penelope Tambama et al. All rights reserved. Detection Progress of Selected Drugs in TLC Thu, 16 Jan 2014 06:49:23 +0000 This entry describes applications of known indicators and dyes as new visualizing reagents and various visualizing systems as well as photocatalytic reactions and bioautography method for the detection of bioactive compounds including drugs and compounds isolated from herbal extracts. Broadening index, detection index, characteristics of densitometric band, modified contrast index, limit of detection, densitometric visualizing index, and linearity range of detected compounds were used for the evaluation of visualizing effects of applied visualizing reagents. It was shown that visualizing effect depends on the chemical structure of the visualizing reagent, the structure of the substance detected, and the chromatographic adsorbent applied. The usefulness of densitometry to direct detection of some drugs was also shown. Quoted papers indicate the detection progress of selected drugs investigated by thin-layer chromatography (TLC). Alina Pyka Copyright © 2014 Alina Pyka. All rights reserved. A Promising Approach to Provide Appropriate Colon Target Drug Delivery Systems of Vancomycin HCL: Pharmaceutical and Microbiological Studies Tue, 14 Jan 2014 10:10:42 +0000 Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10–60% of tablet weight of guar gum (F1–F6) were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6–F20) were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT) values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA) isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6–8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested. Kadria A. Elkhodairy, Samar A. Afifi, and Azza S. Zakaria Copyright © 2014 Kadria A. Elkhodairy et al. All rights reserved. Polymeric Films Loaded with Vitamin E and Aloe vera for Topical Application in the Treatment of Burn Wounds Sun, 12 Jan 2014 00:00:00 +0000 Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns. Gabriela Garrastazu Pereira, Sílvia Stanisçuaki Guterres, Anna Giulia Balducci, Paolo Colombo, and Fabio Sonvico Copyright © 2014 Gabriela Garrastazu Pereira et al. All rights reserved. Pain Management in the Elderly: Transdermal Fentanyl for the Treatment of Pain Caused by Osteoarthritis of the Knee and Hip Sun, 05 Jan 2014 13:17:37 +0000 This study was designed to evaluate the utility of transdermal fentanyl (transdermal fentanyl, TDF) for the treatment of pain due to osteoarthritis (osteoarthritis, OA) of the knee and hip, which was not adequately controlled by nonopioid analgesics or weak opioids. WOMAC is a reliable, valid, and responsive multidimensional, self-administrated outcome measure designed specifically to evaluate patients with OA of the knee or hip. TDF significantly increased pain control and improved functioning and quality of life. Metoclopramide appeared to be of limited value in preventing nausea and vomiting. Sylwester Mordarski Copyright © 2014 Sylwester Mordarski. All rights reserved. Formulation and Evaluation of Fixed-Dose Combination of Bilayer Gastroretentive Matrix Tablet Containing Atorvastatin as Fast-Release and Atenolol as Sustained-Release Thu, 02 Jan 2014 13:00:44 +0000 The objective of the present study was to develop bilayer tablets of atorvastatin and atenolol that are characterized by initial fast-release of atorvastatin in the stomach and comply with the release requirements of sustained-release of atenolol. An amorphous, solvent evaporation inclusion complex of atorvastatin with β-cyclodextrin, present in 1 : 3 (drug/cyclodextrin) molar ratio, was employed in the fast-release layer to enhance the dissolution of atorvastatin. Xanthan gum and guar gum were integrated in the sustained-release layer. Bilayer tablets composed of sustained-release layer (10% w/w of xanthan gum and guar gum) and fast-release layer [1 : 3 (drug/cyclodextrin)] showed the desired release profile. The atorvastatin contained in the fast-release layer showed an initial fast-release of more than 60% of its drug content within 2 h, followed by sustained release of the atenolol for a period of 12 h. The pharmacokinetic study illustrated that the fast absorption and increased oral bioavailability of atorvastatin as well as therapeutic concentration of atenolol in blood were made available through adoption of formulation strategy of bilayer tablets. It can be concluded that the bilayer tablets of atorvastatin and atenolol can be successfully employed for the treatment of hypertension and hypercholesterolemia together through oral administration of single tablet. Sanjay Dey, Sankha Chattopadhyay, and Bhaskar Mazumder Copyright © 2014 Sanjay Dey et al. All rights reserved. Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates Thu, 05 Dec 2013 13:44:31 +0000 We previously reported the synthesis of three DOX conjugates that represented different targeting vehicles and showed them to have antitumor activity both in vitro and in vivo. However, the relationships between the pharmacokinetics of these DOX conjugates and their chemical structures were not characterized. In the current study, free DOX derived from each of the conjugates was found at low levels in the rat circulatory system, with conjugated DOX being the major form. The two polyethylene glycol (PEG) conjugates slowly released DOX, and 1/2β for total DOX from DOX-LNA, PEG-ami-DOX, and PEG-hyd-DOX was 5.79, 10.22, and 15.18 h, respectively. All three conjugates also deposited less DOX into normal organs than did an equivalent dose of free DOX, and the value of free DOX released by DOX- LNA, PEG-ami-DOX, and PEG-hyd-DOX was 32.5, 9.5, and 4.7 μg/g, respectively. Among the conjugates, the compound with an acid-labile bond between PEG and DOX exhibited the lowest free DOX deposition in healthy tissues, which should decrease the systemic toxicity of free DOX while allowing for tumor targeting by PEG. Menglei Huan, Shuang Tian, Han Cui, Bangle Zhang, Dan Su, Jieping Wang, Kangchu Li, and Weidong Cao Copyright © 2013 Menglei Huan et al. All rights reserved. Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging Wed, 04 Dec 2013 13:58:42 +0000 The aging process causes a number of changes in the skin, including oxidative stress and dyschromia. The kojic acid (KA) is iron chelator employed in treatment of skin aging, and inhibits tyrosinase, promotes depigmentation. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can modulate drug permeation through the skin and improve the drug activity. This study is aimed at structurally developing and characterizing a kojic acid-loaded LCS, consists of water (W), cetostearyl isononanoate (oil—O) and PPG-5-CETETH-20 (surfactant-S) and evaluating its in vitro skin permeation and retention. Three regions of the diagram were selected for characterization: A (35% O, 50% S, 15% W), B (30% O, 50% S, 20% W) and C (20% O, 50% S, 30% W), to which 2% KA was added. The formulations were subjected to polarized light microscopy, which indicated the presence of a hexagonal mesophase. Texture and bioadhesion assay showed that formulation B is suitable for topical application. According to the results from the in vitro permeation and retention of KA, the formulations developed can modulate the permeation of KA in the skin. The in vitro cytotoxic assays showed that KA-unloaded LCS and KA-loaded LCS didn't present cytotoxicity. PPG-5-CETETH-20-based systems may be a promising platform for KA skin delivery. M. L. Gonçalez, M. A. Corrêa, and M. Chorilli Copyright © 2013 M. L. Gonçalez et al. All rights reserved. Liposomes-in-Hydrogel Delivery System with Mupirocin: In Vitro Antibiofilm Studies and In Vivo Evaluation in Mice Burn Model Thu, 28 Nov 2013 11:39:41 +0000 Previously, we have proposed mupirocin-in-liposomes-in-hydrogel delivery system as advanced delivery system with the potential in treatment of burns. In the current studies, we evaluated the system for its cytotoxicity, ability to prevent biofilm formation, act on the mature biofilms, and finally determined its potential as wound treatment in in vivo mice burn model. The system was found to be nontoxic against HaCaT cells, that is, keratinocytes. It was safe for use and exhibited antibiofilm activity against S. aureus biofilms, although the activity was more significant against planktonic bacteria and prior to biofilm formation than against mature biofilms as shown in the resazurin and the crystal violet assays. An in vivo mice burn model was used to evaluate the biological potential of the system and the healing of burns observed over 28 days. The in vivo data suggest that the delivery system enhances wound healing and is equally potent as the marketed product of mupirocin. Histological examination showed no difference in the quality of the healed scar tissue, whereas the healing time for the new delivery system was shorter as compared to the marketed product. Further animal studies and development of more sophisticated in vivo model are needed for complete evaluation. Julia Hurler, Karen K. Sørensen, Adyary Fallarero, Pia Vuorela, and Nataša Škalko-Basnet Copyright © 2013 Julia Hurler et al. All rights reserved. Prolonged Delivery of Ciprofloxacin and Diclofenac Sodium from a Polymeric Fibre Device for the Treatment of Peridontal Disease Thu, 14 Nov 2013 15:44:21 +0000 In vitro analysis of drug release and antimicrobial activity of the coblended crosslinked polymeric fibre device (PFD) were investigated. The fibre loaded with ciprofloxacin and diclofenac sodium was comprised of alginate and glycerol crosslinked with barium cations. The pH dependent drug release was evident with ciprofloxacin and diclofenac sodium diffusing from the fibre at pH 4.0 compared to pH 6.8, where the fibre swelled and eroded resulting in zero-order drug release. Agar diffusion studies followed by minimum inhibitory assays were conducted to determine the antimicrobial activity of the device against Escherichia coli, Enterococcus faecalis, and Streptococcus mutans. The antimicrobial activity of the PFD was confirmed in both test assays against all test pathogens. The MIC ranges at pH 4.0 for E. coli, E. faecalis, and S. mutans were 0.5–0.8, 0.4–1.1, and 0.7–2.1 g/mL, respectively. At pH 6.8, similar efficacies (0.3–0.5 g/mL for E. coli and E. faecalis and 0.6–1.0 g/mL for S. mutans) were observed. The effect of varying the plasticizer and crosslinking ion concentration on drug release profile of the fibers was further elucidated and conceptualized using molecular mechanics energy relationships (MMER) and by exploring the spatial disposition of geometrically minimized molecular conformations. Deanne Johnston, Yahya E. Choonara, Pradeep Kumar, Lisa C. du Toit, Sandy van Vuuren, and Viness Pillay Copyright © 2013 Deanne Johnston et al. All rights reserved. A pH-Sensitive, Biobased Calcium Carbonate Aragonite Nanocrystal as a Novel Anticancer Delivery System Thu, 14 Nov 2013 10:48:44 +0000 The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO3/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO3/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO3/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO3 nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy. Abdullahi Shafiu Kamba, Maznah Ismail, Tengku Azmi Tengku Ibrahim, and Zuki Abu Bakar Zakaria Copyright © 2013 Abdullahi Shafiu Kamba et al. All rights reserved. Gelucire Based In Situ Gelling Emulsions: A Potential Carrier for Sustained Stomach Specific Delivery of Gastric Irritant Drugs Sun, 10 Nov 2013 15:21:42 +0000 Non steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed medications to the geriatric patients for the treatment of arthritis and other painful disorders. The major side effects of NSAIDs are related to their effects on the stomach and bowels. The present study concerns assessment of the potential of liquid in situ gelling emulsion formulations (emulgels) as patient compliant stomach specific sustained release carrier for the delivery of highly gastric irritant drug, Piroxicam. Emulgels were prepared, without using any emulgent, by mixing different concentrations of molten Gelucire 39/01 with low viscosity sodium alginate solution prepared in deionized water at 50°C. CaCO3 was used as buoyancy imparting as well as crosslinking agent. Emulgels so prepared were homogenous, physically stable, and rapidly formed into buoyant gelled mass when exposed to simulated gastric fluid (SGF, pH 1.2). Drug release studies carried out in SGF revealed significant retardation () of Piroxicam release from emulgels compared to conventional in situ gelling formulations prepared without Gelucire 39/01. Pharmacodynamic studies carried out in albino rats revealed significantly increased analgesic/anti-inflammatory response from in situ emulgels compared to conventional in situ gelling formulations. Further, in vivo toxicity studies carried out in albino rats revealed no signs of gastric ulceration upon prolonged dosing. Ashwin Saxena, Arun K. Mishra, Navneet Verma, Shiv S. Bhattacharya, Amitava Ghosh, Anurag Verma, and Jayanta K. Pandit Copyright © 2013 Ashwin Saxena et al. All rights reserved. Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol Sun, 10 Nov 2013 13:30:36 +0000 The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. Swati C. Jagdale, Nilesh A. Bari, Bhanudas S. Kuchekar, and Aniruddha R. Chabukswar Copyright © 2013 Swati C. Jagdale et al. All rights reserved. Novel Poly(L-lactide-co-ε-caprolactone) Matrices Obtained with the Use of Zr[Acac]4 as Nontoxic Initiator for Long-Term Release of Immunosuppressive Drugs Mon, 28 Oct 2013 14:35:40 +0000 Slowly degradable copolymers of L-lactide and ε-caprolactone can provide long-term delivery and may be interesting as alternative release systems of cyclosporine A (CyA) and rapamycin (sirolimus), in which available dosage forms cause a lot of side effects. The aim of this study was to obtain slowly degradable matrices containing immunosuppressive drug from PLACL initiated by nontoxic Zr[Acac]4. Three kinds of poly(L-lactide-co-ε-caprolactone) (PLACL) matrices with different copolymer chain microstructure were used to compare the release process of cyclosporine A and rapamycine. The influence of copolymer chain microstructure on drug release rate and profile was also analyzed. The determined parameters could be used to tailor drug release by synthesis of demanded polymeric drug carrier. The studied copolymers were characterized at the beginning and during the degradation process of the polymeric matrices by NMR spectroscopy, GPC (gel permeation chromatography), and DSC (differential scanning calorimetry). Different drug release profiles have been observed from each kind of copolymer. The correlation between drug release process and changes of copolymer microstructure during degradation process was noticed. It was determined that different copolymer composition (e.g., lower amount of caprolactone units) does not have to influence the drug release, but even small changes in copolymer randomness affect this process. Katarzyna Jelonek, Janusz Kasperczyk, Suming Li, Piotr Dobrzynski, Henryk Janeczek, and Bozena Jarzabek Copyright © 2013 Katarzyna Jelonek et al. All rights reserved. Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance Mon, 28 Oct 2013 13:35:54 +0000 Liver is a vital organ responsible for plethora of functions including detoxification, protein synthesis, and the production of biochemicals necessary for the sustenance of life. Therefore, patients with chronic liver diseases such as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate attention to sustain life and as a result are often exposed to the prolonged treatment with drugs/herbal medications. Lack of site-specific delivery of these medications to the hepatocytes/nonparenchymal cells and adverse effects associated with their off-target interactions limit their continuous use. This calls for the development and fabrication of targeted delivery systems which can deliver the drug payload at the desired site of action for defined period of time. The primary aim of drug targeting is to manipulate the whole body distribution of drugs, that is, to prevent distribution to non-target cells and concomitantly increase the drug concentration at the targeted site. Carrier molecules are designed for their selective cellular uptake, taking advantage of specific receptors or binding sites present on the surface membrane of the target cell. In this review, various aspects of liver targeting of drug molecules and herbal medications have been discussed which elucidate the importance of delivering the drugs/herbal medications at their desired site of action. Nidhi Mishra, Narayan Prasad Yadav, Vineet Kumar Rai, Priyam Sinha, Kuldeep Singh Yadav, Sanyog Jain, and Sumit Arora Copyright © 2013 Nidhi Mishra et al. All rights reserved. Characterization of the Phytochemical Constituents of Taif Rose and Its Antioxidant and Anticancer Activities Sun, 27 Oct 2013 15:12:34 +0000 Ward Taifi (Taif rose) is considered one of the most important economic products of Taif, Saudi Arabia. In this study both fresh and dry Taif rose were biologically and phytochemically investigated. The 80% methanol extracts and -butanol fractions of dry and fresh Taif rose had high radical scavenging activity toward artificial 1,1-diphenyl picrylhydrazyl (DPPH)• radical with SC50 values range 5.86−12.24 µg/ml whereas the aqueous fractions showed weak activity. All samples had in vitro anticancer activity toward HepG2 with IC50 < 20 µg/ml which fall within the criteria of the American Cancer Institute. High positive correlation appeared between the antioxidant activity and total phenolics whereas there is no correlation between total phenolics and anticancer activity. The LC-ESI(− ve)-MS analysis of all extracts indicate the presence of phenolic compounds belonging to hydrolysable tannins and flavonol glycosides. In conclusion, the presence of this is considered to be the first phytochemical report that identifies the major compounds in dry and fresh roses using HPLC-ESI-MS. The methanol extracts and its -butanol and aqueous fractions for both fresh and dry Taif rose could be used as preventive and therapeutic effective natural agents for diseases in which free radicals involved after more in vitro and in vivo studies. El-Sayed S. Abdel-Hameed, Salih A. Bazaid, and Mahmood S. Salman Copyright © 2013 El-Sayed S. Abdel-Hameed et al. All rights reserved. Folic Acid-Chitosan Conjugated Nanoparticles for Improving Tumor-Targeted Drug Delivery Sat, 26 Oct 2013 14:24:16 +0000 Objective. To prepare folic acid-chitosan conjugated nanoparticles (FA-CS NPs) and evaluate their targeting specificity on tumor cells. Methods. Chitosan (CS) NPs were prepared by ionic cross linking method, and folic acid (FA) was conjugated with CS NPs by electrostatic interaction. The properties of NPs were investigated, and doxorubicin hydrochloride (Dox) as a model drug was encapsulated for investigating drug release pattern in vitro. The cytotoxicity and cellular uptake of FA-CS NPs were also investigated. Results. The results reveal that the obtained FA-CS NPs were monodisperse nanoparticles with suitable average size and positive surface charge. Dox was easily loaded into FA-CS NPs, and the release pattern showed a long and biphasic drug release. Noticeable phagocytosis effect was observed in the presence of rhodamine B-labeled FA-CSNPs when incubating with the folate receptor-positive SMMC-7221 cells. Conclusion. Compared with the unmodified CS NPs, FA-CS NPs showed much higher cell uptaking ability due to the known folate-receptor mediated endocytosis. FA-CS NPs provide a potential way to enhance the using efficiency of antitumor drug by folate receptor mediated targeting delivery. Huijuan Song, Chang Su, Wenyu Cui, Bingya Zhu, Liwei Liu, Zhenhua Chen, and Liang Zhao Copyright © 2013 Huijuan Song et al. All rights reserved. Colon Targeted Guar Gum Compression Coated Tablets of Flurbiprofen: Formulation, Development, and Pharmacokinetics Thu, 24 Oct 2013 16:10:27 +0000 The rationale of the present study is to formulate flurbiprofen colon targeted compression coated tablets using guar gum to improve the therapeutic efficacy by increasing drug levels in colon, and also to reduce the side effects in upper gastrointestinal tract. Direct compression method was used to prepare flurbiprofen core tablets, and they were compression coated with guar gum. Then the tablets were optimized with the support of in vitro dissolution studies, and further it was proved by pharmacokinetic studies. The optimized formulation (F4) showed almost complete drug release in the colon (99.86%) within 24 h without drug loss in the initial lag period of 5 h (only 6.84% drug release was observed during this period). The pharmacokinetic estimations proved the capability of guar gum compression coated tablets to achieve colon targeting. The Cmax of colon targeted tablets was 11956.15 ng/mL at Tmax of 10 h whereas it was 15677.52 ng/mL at 3 h in case of immediate release tablets. The area under the curve for the immediate release and compression coated tablets was 40385.78 and 78214.50 ng-h/mL and the mean resident time was 3.49 and 10.78 h, respectively. In conclusion, formulation of guar gum compression coated tablets was appropriate for colon targeting of flurbiprofen. Sateesh Kumar Vemula and Vijaya Kumar Bontha Copyright © 2013 Sateesh Kumar Vemula and Vijaya Kumar Bontha. All rights reserved. Prostaglandin Analogous and Antioxidant Activity Mediated Gastroprotective Action of Tabernaemontana divaricata (L.) R. Br. Flower Methanolic Extract against Chemically Induced Gastric Ulcers in Rats Thu, 24 Oct 2013 09:11:42 +0000 The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses—125, 250, and 500 mg/kg—orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization—high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous. Mohammed Safwan Ali Khan, Abdul Manan Mat Jais, and Adiba Afreen Copyright © 2013 Mohammed Safwan Ali Khan et al. All rights reserved. Development and Evaluation of Solid Lipid Nanoparticles of Raloxifene Hydrochloride for Enhanced Bioavailability Sun, 20 Oct 2013 15:10:33 +0000 Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug. In vitro drug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and DSC studies indicated no interaction between drug and lipid, and the XRD spectrum showed that RL-HCL is in amorphous form in the formulation. In vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics. Pharmacokinetics of raloxifene loaded solid lipid nanoparticles after oral administration to Wistar rats was studied. Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL-HCL. Anand Kumar Kushwaha, Parameswara Rao Vuddanda, Priyanka Karunanidhi, Sanjay Kumar Singh, and Sanjay Singh Copyright © 2013 Anand Kumar Kushwaha et al. All rights reserved. Release of a Wound-Healing Agent from PLGA Microspheres in a Thermosensitive Gel Thu, 03 Oct 2013 17:30:09 +0000 The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4–7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant consideration and testing in animal wound models for treating combat-related injuries. H. A. Machado, J. J. Abercrombie, T. You, P. P. DeLuca, and K. P. Leung Copyright © 2013 H. A. Machado et al. All rights reserved. Phytoestrogen α-Zearalanol Attenuates Homocysteine-Induced Apoptosis in Human Umbilical Vein Endothelial Cells Tue, 01 Oct 2013 09:05:16 +0000 Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. The enhanced nitrative stress plays an important role in homocysteine-induced endothelial dysfunction. Previous studies have showed that phytoestrogen α-zearalanol alleviated endothelial injury in ovariectomized hyperhomocysteinemic rats; however, the underlying mechanism remains to be clarified. This study was to investigate the effects of α-zearalanol on homocysteine-induced endothelial apoptosis in vitro and explore the possible role of nitrative stress in these effects. Results showed that homocysteine (500 μmol/L, 24 h) induced the apoptosis of human umbilical vein endothelial cells (HUVECs) obviously, and this effect was significantly attenuated by pretreatment with α-zearalanol (10−8~10−6 mol/L). Moreover, α-zearalanol downregulated proapoptotic protein Bax, upregulated antiapoptotic proteins Bcl-2 and Bcl-XL, and decreased the expression and activity of caspase-9. These findings demonstrated that α-zearalanol could effectively alleviate homocysteine-induced endothelial apoptosis, and this antiapoptosis effect might be related to the inhibition of the intrinsic pathway. Western blot indicated an enhanced 3-nitrotyrosine expression in HUVECs when challenged with homocysteine, which was attenuated by pretreatment with α-zearalanol. This result implied that inhibition of nitrative stress might play a role in the protective effect of α-zearalanol on endothelial cells. Such discovery may shed a novel light on the antiatherogenic activities of α-zearalanol in hyperhomocysteinemia. Teng Liu, Dan-dan Hou, Qian Zhao, Wei Liu, Pan-pan Zhen, Jian-ping Xu, Ke Wang, Hai-xia Huang, Xiao Li, Hui Zhang, Hai-bo Xu, and Wen Wang Copyright © 2013 Teng Liu et al. All rights reserved. STAT6 siRNA Matrix-Loaded Gelatin Nanocarriers: Formulation, Characterization, and Ex Vivo Proof of Concept Using Adenocarcinoma Cells Thu, 26 Sep 2013 15:34:32 +0000 The clinical utility of siRNA therapy has been hampered due to poor cell penetration, nonspecific effects, rapid degradation, and short half-life. We herewith proposed the formulation development of STAT6 siRNA (S6S) nanotherapeutic agent by encapsulating them within gelatin nanocarriers (GNC). The prepared nanoformulation was characterized for size, charge, loading efficiency, release kinetics, stability, cytotoxicity, and gene silencing assay. The stability of S6S-GNC was also assessed under conditions of varying pH, serum level, and using electrophoretic assays. In vitro cytotoxicity performance was evaluated in human adenocarcinoma A549 cells following MTT assay. The developed formulation resulted in an average particle size, surface charge, and encapsulation efficiency as  nm,  mV, and , respectively. S6S-GNC showed an insignificant () change in the size and charge in the presence of buffer solutions (pH 6.4 to 8.4) and FBS (10% v/v). A549 cells were treated with native S6S, S6S-lipofectamine, placebo-GNC, and S6S-GNC using untreated cells as a control. It was observed that cell viability was decreased significantly with S6S-GNC by () compared to native S6S (%) and S6S-lipofectamine complex (. This investigation infers that gelatin polymer-based nanocarriers are a robust, stable, and biocompatible strategy for the delivery of siRNA. Susanne R. Youngren, Rakesh K. Tekade, Brianne Gustilo, Peter R. Hoffmann, and Mahavir B. Chougule Copyright © 2013 Susanne R. Youngren et al. All rights reserved. Formulation and Evaluation of Chitosan-Chondroitin Sulphate Based Nasal Inserts for Zolmitriptan Tue, 24 Sep 2013 15:27:23 +0000 Bioadhesive nasal dosage forms are an attractive method for overcoming rapid mucociliary clearance transport in the nose and for delivering the drug directly to brain. The present study was designed to formulate chondroitin sulphate (CS) and chitosan (CH) nasal inserts employing zolmitriptan, an antimigraine drug. The interpolymer complexes (IPC) formed between –COO− and – groups of CS and group of CH were characterized by infrared spectroscopy (IR), differential scanning analysis (DSC), and zeta potential studies. The unloaded and loaded nasal inserts were evaluated for water uptake studies, and bioadhesive strength studies, scanning electron microscopic studies (SEM). The in vitro drug release and in situ permeation studies were carried out on loaded nasal inserts. The DSC and IR studies confirmed the formation of a complex between the two polymers. The results indicated that the formulation F1 (CH : CS; 30 : 70) was demonstrating the highest bioadhesive strength and zeta potential. The presence of porous structure in the nasal inserts was confirmed by the SEM analysis. Further, in vitro and in situ release studies demonstrated that formulations F9 and F11 (drug : polymer; 1 : 10) were releasing 90% and 98% zolmitriptan over a period of 8 h. It can be concluded that nasal inserts formulated from chitosan-chondroitin sulphate (CH-CS) interpolymer complex (IPC) can be used for delivery of antimigraine drug to brain. Kirandeep Kaur and Gurpreet Kaur Copyright © 2013 Kirandeep Kaur and Gurpreet Kaur. All rights reserved. Anti-Inflammatory Activity of Bioaccessible Fraction from Eryngium foetidum Leaves Tue, 17 Sep 2013 09:41:59 +0000 Eryngium foetidum (EF) has long been used as a medicinal plant and culinary spice in tropical regions. Phytochemicals in its leaves have been proposed to be responsible for the anti-inflammatory and antioxidant activities. The present study used in vitro digestion coupled with Caco-2 cells to assess such activities. Caco-2 cells were incubated with aqueous fraction from simulated digestion (bioaccessible fraction) of EF leaves with/without bile extract prior to stimulation with interleukin-1 beta (IL-1). Monocyte chemoattractant protein-1 (MCP-1) and IL-8 in culture media and the intracellular reactive oxygen species (ROS) were measured. Approximately 24% -carotene and 35% lutein of leaves were present in the aqueous fraction. The transfer of caffeic and chlorogenic acids to the aqueous fraction was 76%–81%, while that of kaempferol was 48%. Prior incubation of Caco-2 cells with the bioaccessible fraction suppressed IL-1 activated IL-8 and MCP-1 by 33%, but the fraction lacking mixed micelles decreased IL-8 and MCP-1 levels only by 11%. The pretreatment of Caco-2 cells with the bioaccessible fraction of EF reduced ROS by 34%; the fraction lacking mixed micelles decreased ROS by 28%. These data suggest that bioactive compounds partitioning in mixed micelles play a significant role to suppress the proinflammatory insult but with a modest antioxidant effect. Suwitcha Dawilai, Chawanphat Muangnoi, Phawachaya Praengamthanachoti, and Siriporn Tuntipopipat Copyright © 2013 Suwitcha Dawilai et al. All rights reserved. Pharmacokinetics and Bioequivalence Evaluation of Cyclobenzaprine Tablets Mon, 16 Sep 2013 11:56:20 +0000 The purpose of this study was to investigate cyclobenzaprine pharmacokinetics and to evaluate bioequivalence between two different tablet formulations containing the drug. An open, randomized, crossover, single-dose, two-period, and two-sequence design was employed. Tablets were administered to 23 healthy subjects after an overnight fasting and blood samples were collected up to 240 hours after drug administration. Plasma cyclobenzaprine was quantified by means of an LC-MS/MS method. Pharmacokinetic parameters related to absorption, distribution, and elimination were calculated. Cyclobenzaprine plasma profiles for the reference and test products were similar, as well as absorption pharmacokinetic parameters AUC (reference: 199.4 ng∗h/mL; test: 201.6 ng∗h/mL), (reference: 7.0 ng/mL; test: 7.2 ng/mL), and (reference: 4.5 h; test: 4.6 h). Bioequivalence was evaluated by means of 90% confidence intervals for the ratio of AUC (93%–111%) and (93%–112%) values for test and reference products, which were within the 80%–125% interval proposed by FDA. Cyclobenzaprine pharmacokinetics can be described by a multicompartment open model with an average rapid elimination half-life () of 3.1 hours and an average terminal elimination half-life () of 31.9 hours. Tatiane Maria de Lima Souza Brioschi, Simone Grigoleto Schramm, Eunice Kazue Kano, Eunice Emiko Mori Koono, Ting Hui Ching, Cristina Helena dos Reis Serra, and Valentina Porta Copyright © 2013 Tatiane Maria de Lima Souza Brioschi et al. All rights reserved. Formulation Development and Evaluation of Hybrid Nanocarrier for Cancer Therapy: Taguchi Orthogonal Array Based Design Wed, 11 Sep 2013 15:10:45 +0000 Taguchi orthogonal array design is a statistical approach that helps to overcome limitations associated with time consuming full factorial experimental design. In this study, the Taguchi orthogonal array design was applied to establish the optimum conditions for bovine serum albumin (BSA) nanocarrier (ANC) preparation. Taguchi method with L9 type of robust orthogonal array design was adopted to optimize the experimental conditions. Three key dependent factors namely, BSA concentration (% w/v), volume of BSA solution to total ethanol ratio (v : v), and concentration of diluted ethanolic aqueous solution (% v/v), were studied at three levels 3%, 4%, and 5% w/v; 1 : 0.75, 1 : 0.90, and 1 : 1.05 v/v; 40%, 70%, and 100% v/v, respectively. The ethanolic aqueous solution was used to impart less harsh condition for desolvation and attain controlled nanoparticle formation. The interaction plot studies inferred the ethanolic aqueous solution concentration to be the most influential parameter that affects the particle size of nanoformulation. This method (BSA, 4% w/v; volume of BSA solution to total ethanol ratio, 1 : 0.90 v/v; concentration of diluted ethanolic solution, 70% v/v) was able to successfully develop Gemcitabine (G) loaded modified albumin nanocarrier (M-ANC-G) of size  nm ( mV) as against to  nm ( mV) using conventional method albumin nanocarrier (C-ANC-G). Hybrid nanocarriers were generated by chitosan layering (solvent gelation technique) of respective ANC to form C-HNC-G and M-HNC-G of sizes nm ( mV) and  nm ( mV), respectively. Zeta potential, entrapment, in vitro release, and pH-based stability studies were investigated and influence of formulation parameters are discussed. Cell-line-based cytotoxicity assay (A549 and H460 cells) and cell internalization assay (H460 cell line) were performed to assess the influence on the bioperformance of these nanoformulations. Rakesh K. Tekade and Mahavir B. Chougule Copyright © 2013 Rakesh K. Tekade and Mahavir B. Chougule. All rights reserved. Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets Sun, 08 Sep 2013 09:59:53 +0000 The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at °C and % relative humidity), and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo. Paulo Renato Oliveira, Cassiana Mendes, Lilian Klein, Maximiliano da Silva Sangoi, Larissa Sakis Bernardi, and Marcos Antônio Segatto Silva Copyright © 2013 Paulo Renato Oliveira et al. All rights reserved. Development and Characterization of Novel Polyurethane Films Impregnated with Tolfenamic Acid for Therapeutic Applications Sun, 01 Sep 2013 13:37:37 +0000 The present study deals with the preparation of polyurethane (PU) films impregnated with a nonsteroidal anti-inflammatory drug, tolfenamic acid (TA). Solvent evaporation technique has been employed for the preparation of TA-PU films in two different ratios of 1 : 2 and 1 : 5 in Tetrahydrofuran (THF) or THF-ethanol mixtures. The prepared films were characterized using X-Ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and release studies. The results indicate transformation of crystalline TA to its amorphous form. The degree of crystallinity changes both by increasing the polymer concentration and solvent used for the film preparations. The release profiles of TA were also found to be affected, showing a decrease from approximately 50% to 25% from 1 : 2 to 1 : 5 ratios, respectively. Hilal Istanbullu, Sofia Ahmed, Muhammad Ali Sheraz, and Ihtesham ur Rehman Copyright © 2013 Hilal Istanbullu et al. All rights reserved. Protective Effect of Fermented Soybean Dried Extracts against TPA-Induced Oxidative Stress in Hairless Mice Skin Thu, 29 Aug 2013 15:57:17 +0000 This study evaluated the chemical properties (polyphenol and genistein contents) of soybean extracts obtained by biotransformation and dried by spray dryer at different conditions and their in vivo ability to inhibit 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced biochemical alterations in the skin of hairless mice. By comparing the obtained data with that of the well-known active soybean extract Isoflavin beta, we evaluated the influence of the fermentation and drying process in the extracts efficacy. The results demonstrated that inlet gas temperature and adjuvant concentration for the extract drying process have significantly affected the total polyphenol contents and, to a minor degree, the genistein contents. However, the effect of topical stimulus with TPA, an oxidative stress inducer, which caused significant depletion of reduced glutathione (GSH) and catalase, with increased levels of H2O2 and lipid peroxidation (MDA) in the skin of hairless mice, was significantly prevented by the soybean extracts treatment. These results indicate that the spray drying processing resulted in a product capable of limiting the oxidative stress with possible therapeutic applicability as an antioxidant in pharmaceutical forms. Sandra R. Georgetti, Rúbia Casagrande, Fabiana T. M. C. Vicentini, Marcela M. Baracat, Waldiceu A. Verri Jr., and Maria J. V. Fonseca Copyright © 2013 Sandra R. Georgetti et al. All rights reserved. Comparative Plasma Exposure of Albendazole after Administration of Rapidly Disintegrating Tablets in Dogs Sun, 25 Aug 2013 10:13:30 +0000 The main objectives of this study were (a) to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b) to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form. Silvina G. Castro, Alicia Dib, Gonzalo Suarez, Daniel Allemandi, Carlos Lanusse, Sergio Sanchez Bruni, and Santiago D. Palma Copyright © 2013 Silvina G. Castro et al. All rights reserved. Validation Thin Layer Chromatography for the Determination of Acetaminophen in Tablets and Comparison with a Pharmacopeial Method Sun, 25 Aug 2013 09:36:32 +0000 Adsorption thin layer chromatography (NP-TLC) with densitometry has been established for the identification and the quantification of acetaminophen in three leading commercial products of pharmaceutical tablets coded as brand: P1 (Product no. 1), P2 (Product no. 2), and P3 (Product no. 3). Applied chromatographic conditions have separated acetaminophen from its related substances, namely, 4-aminophenol and and 4′-chloroacetanilide. UV densitometry was performed in absorbance mode at 248 nm. The presented method was validated by specificity, range, linearity, accuracy, precision, detection limit, quantitative limit, and robustness. The TLC-densitometric method was also compared with a pharmacopeial UV-spectrophotometric method for the assay of acetaminophen, and the results confirmed statistically that the NP-TLC-densitometric method can be used as a substitute method. It could be said that the validated NP-TLC-densitometric method is suitable for the routine analysis of acetaminophen in quantity control laboratories. Alina Pyka, Marika Budzisz, and Małgorzata Dołowy Copyright © 2013 Alina Pyka et al. All rights reserved. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery Sat, 24 Aug 2013 09:39:52 +0000 Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile. Praveen Kumar Gaur, Shikha Mishra, and Suresh Purohit Copyright © 2013 Praveen Kumar Gaur et al. All rights reserved. Enhanced Topical Delivery of Tetrandrine by Ethosomes for Treatment of Arthritis Sat, 24 Aug 2013 09:29:13 +0000 The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base () with pH-dependent partition coefficient. The spherical-shaped ethosomes were prepared by pH gradient loading method. Ex vivo permeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund’s complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin. Chao Fan, Xinru Li, Yanxia Zhou, Yong Zhao, Shujin Ma, Wenjing Li, Yan Liu, and Guiling Li Copyright © 2013 Chao Fan et al. All rights reserved. A Novel Multilayered Multidisk Oral Tablet for Chronotherapeutic Drug Delivery Tue, 20 Aug 2013 13:55:57 +0000 A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery. Zaheeda Khan, Yahya E. Choonara, Pradeep Kumar, Lisa C. du Toit, Valence M. K. Ndesendo, and Viness Pillay Copyright © 2013 Zaheeda Khan et al. All rights reserved. Sonication-Based Improvement of the Physicochemical Properties of Guar Gum as a Potential Substrate for Modified Drug Delivery Systems Mon, 05 Aug 2013 08:49:16 +0000 Guar Gum is a natural polysaccharide that, due to its physicochemical properties, is extensively investigated for biomedical applications as a matrix for modified drug delivery, but it is also used in the food industry as well as in cosmetics. A commercial sample of Guar Gum was sonicated for different periods of time, and the reduction in the average molecular weight was monitored by means of viscometric measurements. At the same time, the rheological behaviour was also followed, in terms of viscoelasticity range, flow curves, and mechanical spectra. Sonicated samples were used for the preparation of gels in the presence of borate ions. The effect of borax on the new samples was investigated by recording mechanical spectra, flow curves, and visible absorption spectra of complexes with Congo Red. The anisotropic elongation, observed in previous studies with tablets of Guar Gum and borax, was remarkably reduced when the sonicated samples were used for the preparation of the gels. Siddique Akber Ansari, Pietro Matricardi, Claudia Cencetti, Chiara Di Meo, Maria Carafa, Claudia Mazzuca, Antonio Palleschi, Donatella Capitani, Franco Alhaique, and Tommasina Coviello Copyright © 2013 Siddique Akber Ansari et al. All rights reserved. Development of Bioadhesive Chitosan Superporous Hydrogel Composite Particles Based Intestinal Drug Delivery System Sun, 04 Aug 2013 10:35:36 +0000 Bioadhesive superporous hydrogel composite (SPHC) particles were developed for an intestinal delivery of metoprolol succinate and characterized for density, porosity, swelling, morphology, and bioadhesion studies. Chitosan and HPMC were used as bioadhesive and release retardant polymers, respectively. A 32 full factorial design was applied to optimize the concentration of chitosan and HPMC. The drug loaded bioadhesive SPHC particles were filled in capsule, and the capsule was coated with cellulose acetate phthalate and evaluated for drug content, in vitro drug release, and stability studies. To ascertain the drug release kinetics, the drug release profiles were fitted for mathematical models. The prepared system remains bioadhesive up to eight hours in intestine and showed Hixson-Crowell release with anomalous nonfickian type of drug transport. The application of SPHC polymer particles as a biomaterial carrier opens a new insight into bioadhesive drug delivery system and could be a future platform for other molecules for intestinal delivery. Hitesh Chavda, Ishan Modhia, Anant Mehta, Rupal Patel, and Chhagan Patel Copyright © 2013 Hitesh Chavda et al. All rights reserved. Biodistribution of Amikacin Solid Lipid Nanoparticles after Pulmonary Delivery Thu, 01 Aug 2013 09:14:12 +0000 The main purpose of the present work was studying the biodistribution of amikacin solid lipid nanoparticles (SLNs) after pulmonary delivery to increase its concentration in the lungs for treatment of cystic fibrosis lung infections and also providing a new method for clinical application of amikacin. To achieve this aim, 99mTc labelled amikacin was loaded in cholesterol SLNs and after in vitro optimization, the desired SLNs and free drug were administered through pulmonary and i.v. routes to male rats and qualitative and biodistribution studies were done. Results showed that pulmonary delivery of SLNs of amikacin by microsprayer caused higher drug concentration in lungs than kidneys while i.v. administration of free drug caused reverse conditions. It seems that pulmonary delivery of SLNs may improve patients' compliance due to reduction of drug side effects in kidneys and elongation of drug dosing intervals due to the sustained drug release from SLNs. J. Varshosaz, S. Ghaffari, S. F. Mirshojaei, A. Jafarian, F. Atyabi, F. Kobarfard, and S. Azarmi Copyright © 2013 J. Varshosaz et al. All rights reserved. Enrichment, Development, and Assessment of Indian Basil Oil Based Antiseptic Cream Formulation Utilizing Hydrophilic-Lipophilic Balance Approach Wed, 31 Jul 2013 09:55:46 +0000 The present work was aimed to develop an antiseptic cream formulation of Indian basil oil utilizing hydrophilic-lipophilic balance approach. In order to determine the required-hydrophilic lipophilic balance (rHLB) of basil oil, emulsions of basil oil were prepared by phase inversion temperature technique using water, Tween 80, and Span 80. Formulated emulsions were assessed for creaming (BE9; 9.8, BE10; 10.2), droplet size (BE18; 3.22 ± 0.09 μm), and turbidity (BE18; 86.12 ± 2.1%). To ensure correctness of the applied methodology, rHLB of light liquid paraffin was also determined. After rHLB determination, basil oil creams were prepared with two different combinations of surfactants, namely, GMS : Tween 80 (1 : 3.45) and SLS : GMS (1 : 3.68), and evaluated for in vitro antimicrobial activity, skin irritation test, viscosity and consistency. The rHLB of basil oil and light liquid paraffin were found to be 13.36 ± 0.36 and 11.5 ± 0.35, respectively. Viscosity, and consistency parameters of cream was found to be consistent over 90 days. Cream formulations showed net zone of growth inhibition in the range of 5.0–11.3 mm against bacteria and 4.3–7.6 mm against fungi. Primary irritation index was found to be between 0.38 and1.05. Conclusively stable, consistent, non-irritant, enriched antiseptic basil oil cream formulations were developed utilizing HLB approach. Narayan Prasad Yadav, Jaya Gopal Meher, Neelam Pandey, Suaib Luqman, Kuldeep Singh Yadav, and Debabrata Chanda Copyright © 2013 Narayan Prasad Yadav et al. All rights reserved. Design and In Vitro Evaluation of a New Nano-Microparticulate System for Enhanced Aqueous-Phase Solubility of Curcumin Sun, 28 Jul 2013 13:26:33 +0000 Curcumin, a yellow polyphenol derived from the turmeric Curcuma longa, has been associated with a diverse therapeutic potential including anti-inflammatory, antioxidant, antiviral, and anticancer properties. However, the poor aqueous solubility and low bioavailability of curcumin have limited its potential when administrated orally. In this study, curcumin was encapsulated in a series of novel nano-microparticulate systems developed to improve its aqueous solubility and stability. The nano-microparticulate systems are based entirely on biocompatible, biodegradable, and edible polymers including chitosan, alginate, and carrageenan. The particles were synthesized via ionotropic gelation. Encapsulating the curcumin into the hydrogel nanoparticles yielded a homogenous curcumin dispersion in aqueous solution compared to the free form of curcumin. Also, the in vitro release profile showed up to 95% release of curcumin from the developed nano-microparticulate systems after 9 hours in PBS at pH 7.4 when freeze-dried particles were used. Diana Guzman-Villanueva, Ibrahim M. El-Sherbiny, Dea Herrera-Ruiz, and Hugh D. C. Smyth Copyright © 2013 Diana Guzman-Villanueva et al. All rights reserved. Tuning Aerosol Particle Size Distribution of Metered Dose Inhalers Using Cosolvents and Surfactants Wed, 24 Jul 2013 08:16:36 +0000 Objectives. The purpose of these studies was to understand the influence of cosolvent and surfactant contributions to particle size distributions emitted from solution metered dose inhalers (pMDIs) based on the propellant HFA 227. Methods. Two sets of formulations were prepared: (a) pMDIs-HFA 227 containing cosolvent (5–15% w/w ethanol) with constant surfactant (pluronic) concentration and (b) pMDIs-HFA 227 containing surfactant (0–5.45% w/w pluronic) with constant cosolvent concentration. Particle size distributions emitted from these pMDIs were analyzed using aerodynamic characterization (inertial impaction) and laser diffraction methods. Results. Both cosolvent and surfactant concentrations were positively correlated with median particle sizes; that is, drug particle size increased with increasing ethanol and pluronic concentrations. However, evaluation of particle size distributions showed that cosolvent caused reduction in the fine particle mode magnitude while the surfactant caused a shift in the mode position. These findings highlight the different mechanisms by which these components influence droplet formation and demonstrate the ability to utilize the different effects in formulations of pMDI-HFA 227 for independently modulating particle sizes in the respirable region. Conclusion. Potentially, the formulation design window generated using these excipients in combination could be used to match the particle size output of reformulated products to preexisting pMDI products. Imran Y. Saleem and Hugh D. C. Smyth Copyright © 2013 Imran Y. Saleem and Hugh D. C. Smyth. All rights reserved. Formulation and Mathematical Optimization of Controlled Release Calcium Alginate Micro Pellets of Frusemide Mon, 22 Jul 2013 11:39:07 +0000 Objective. Frusemide loaded calcium alginate micropellets, an oral microparticulate delivery system, was statistically optimized exhibiting prolonged therapeutic action minimizing its adverse effects. Methods. Ionotropic Gelation technique was adopted employing 32 Factorial designs and keeping the entire process free from organic solvents. Physicochemical and the release characteristics of the prepared formulations were studied, keeping variations only in sodium alginate (primary polymer) and Acrycoat E30D (copolymer) dispersion. Result. Sodium alginate was predominant over Acrycoat E30D in all batches. Nonadditives or interaction was observed to be insignificant. Multiple regressions produced second-order polynomial equation, and the predictive results obtained were validated with high degree of correlation. The in vivo study applauded that optimized calcium alginate micropellets of frusemide can produce a much greater diuretic effect over an extended period of 24 hours. Conclusion. This study reveals that the potential of a single dose of the mathematically optimized micro pellets of frusemide formulation is sufficient in the management of peripheral edema and ascites in congestive heart failure and as well in the treatment of chronic hypertension, leading to better patient compliance, and can be produced with minimum experimentation and time, proving far more cost-effective formulation than the conventional methods of formulating dosage forms. Amitava Ghosh and Prithviraj Chakraborty Copyright © 2013 Amitava Ghosh and Prithviraj Chakraborty. All rights reserved. Enhanced Oral Delivery of Docetaxel Using Thiolated Chitosan Nanoparticles: Preparation, In Vitro and In Vivo Studies Sun, 21 Jul 2013 09:14:49 +0000 The aim of this study was to evaluate a nanoparticulate system with mucoadhesion properties composed of a core of polymethyl methacrylate surrounded by a shell of thiolated chitosan (Ch-GSH-pMMA) for enhancing oral bioavailability of docetaxel (DTX), an anticancer drug. DTX-loaded nanoparticles were prepared by emulsion polymerization method using cerium ammonium nitrate as an initiator. Physicochemical properties of the nanoparticles such as particle size, size distribution, morphology, drug loading, and entrapment efficiency were characterized. The pharmacokinetic study was carried out in vivo using wistar rats. The half-life of DTX-loaded NPs was about 9 times longer than oral DTX used as positive control. The oral bioavailability of DTX was increased to 68.9% for DTX-loaded nanoparticles compared to 6.5% for positive control. The nanoparticles showed stronger effect on the reduction of the transepithelial electrical resistance (TEER) of Caco-2 cell monolayer by opening the tight junctions. According to apparent permeability coefficient () results, the DTX-loaded NPs showed more specific permeation across the Caco-2 cell monolayer in comparison to the DTX. In conclusion, the nanoparticles prepared in this study showed promising results for the development of an oral drug delivery system for anticancer drugs. Shahrooz Saremi, Rassoul Dinarvand, Abbas Kebriaeezadeh, Seyed Nasser Ostad, and Fatemeh Atyabi Copyright © 2013 Shahrooz Saremi et al. All rights reserved. A Comparison between Use of Spray and Freeze Drying Techniques for Preparation of Solid Self-Microemulsifying Formulation of Valsartan and In Vitro and In Vivo Evaluation Thu, 18 Jul 2013 08:35:30 +0000 The objective of the present study was to develop self micro emulsifying formulation (SMEF) of valsartan to improve its oral bioavailability. The formulations were screened on the basis of solubility, stability, emulsification efficiency, particle size and zeta potential. The optimized liquid SMEF contains valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400 (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further, Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the ratio of 2 : 1 and transformed into free flowing powder. Both the optimized liquid and solid SMEF had the particle size <200 nm with rapid reconstitution properties. Both drying methods are equally capable for producing stable solid SMEF and immediate release of drug in in vitro and in vivo conditions. However, the solid SMEF produced by spray drying method showed high flowability and compressibility. The solid state characterization employing the FTIR, DSC and XRD studies indicated insignificant interaction of drug with lipid and adsorbed excipient. The relative bioavailability of solid SMEF was approximately 1.5 to 3.0 folds higher than marketed formulation and pure drug. Thus, the developed solid SMEF illustrates an alternative delivery of valsartan as compared to existing formulations with improved bioavailability. Sanjay Kumar Singh, Parameswara Rao Vuddanda, Sanjay Singh, and Anand Kumar Srivastava Copyright © 2013 Sanjay Kumar Singh et al. All rights reserved. Effects of Nigella sativa and Lepidium sativum on Cyclosporine Pharmacokinetics Tue, 16 Jul 2013 15:24:13 +0000 The present study was conducted to investigate the effects of Nigella sativa and Lepidium sativum on the pharmacokinetics of cyclosporine in rabbits. Two groups of animals were treated separately with Nigella sativa (200 mg/kg p.o.) or Lepidium sativum (150 mg/kg p.o.) for eight consecutive days. On the 8th day, cyclosporine (30 mg/kg p.o.) was administered to each group one hour after herbal treatment. Blood samples were withdrawn at different time intervals (0.0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, and 24 hrs) from marginal ear vein. Cyclosporine was analyzed using UPLC/MS method. The coadministration of Nigella sativa significantly decreased the and of cyclosporine; the change was observed by 35.5% and 55.9%, respectively (). Lepidium sativum did not produce any significant change in of cyclosporine, although its absorption was significantly delayed compared with control group. A remarkable change was observed in and of Lepidium sativum treated group. Our findings suggest that concurrent consumption of Nigella sativa and Lepidium sativum could alter the pharmacokinetics of cyclosporine at various levels. F. I. Al-Jenoobi, S. A. Al-Suwayeh, Iqbal Muzaffar, Mohd Aftab Alam, Khalid M. Al-Kharfy, Hesham M. Korashy, Abdullah M. Al-Mohizea, Abdul Ahad, and Mohd Raish Copyright © 2013 F. I. Al-Jenoobi et al. All rights reserved. New Bioactive Fungal Molecules with High Antioxidant and Antimicrobial Capacity Isolated from Cerrena unicolor Idiophasic Cultures Mon, 15 Jul 2013 14:42:47 +0000 Three bioactive fractions, extracellular laccase (ex-LAC), crude endopolysaccharides (c-EPL), and a low molecular subfraction of secondary metabolites (ex-LMS), were isolated from the idiophasic cultures of the white rot fungus Cerrena unicolor. For the first time, we determined the antioxidant properties of these samples by chemiluminometric measurement (a) and assessment of the scavenging effect on ABTS (b) and the DPPH reduction rate (c). The highest reducing capability was found for the ex-LMS fraction: 39–90% for (a), 20–90% for (b), and 10–59% for (c) at the concentration of 6.25–800 µg/mL. The scavenging abilities of the C. unicolor c-EPL were between 36 and 70% for (a), 2 and 60% for (b), and 28 and 32% for (c) at the concentration of 6.25–800 µg/mL. A very high prooxidative potential was observed for the ex-LAC probes. The preliminary toxicity tests were done using the Microtox system and revealed the following percentage of the toxic effect against Vibrio fischeri: 85.37% for c-EPL, 50.67% for ex-LAC, and 99.8% for ex-LMS, respectively. The ex-LAC sample showed the antibacterial activity against Escherichia coli, c-EPL against Staphylococcus aureus, and ex-LMS against both bacterial strains, respectively, but the stronger inhibitory effect was exerted on S. aureus. Magdalena Jaszek, Monika Osińska-Jaroszuk, Grzegorz Janusz, Anna Matuszewska, Dawid Stefaniuk, Justyna Sulej, Jolanta Polak, Marta Ruminowicz, Krzysztof Grzywnowicz, and Anna Jarosz-Wilkołazka Copyright © 2013 Magdalena Jaszek et al. All rights reserved. Enhanced Transdermal Delivery of Diclofenac Sodium via Conventional Liposomes, Ethosomes, and Transfersomes Sun, 14 Jul 2013 15:15:15 +0000 The aim of this study was to improve the transdermal permeation of Diclofenac sodium, a poorly water-soluble drug, employing conventional liposomes, ethosomes, and transfersomes. The prepared formulations had been characterized for the loaded drug amount and vesicle size. The prepared vesicular systems were incorporated into 1% Carbopol 914 gel, and a survey of in vitro drug release and drug retention into rat skin has been done on them using a modified Franz diffusion cell. The cumulative amount of drug permeated after 24 h, flux, and permeability coefficient were assessed. Stability studies were performed for three months. The size of vesicles ranged from 145 to 202 nm, and the encapsulation efficiency of the Diclofenac sodium was obtained between 42.61% and 51.72%. The transfersomes and ethosomes provided a significantly higher amount of cumulative permeation, steady state flux, permeability coefficient, and residual drug into skin compared to the conventional liposomes, conventional gel, or hydroethanolic solution. The in vitro release data of all vesicular systems were well fit into Higuchi model (RSD > 0.99). Stability tests indicated that the vesicular formulations were stable over three months. Results revealed that both ethosome and transfersome formulations can act as drug reservoir in skin and extend the pharmacologic effects of Diclofenac sodium. Saeed Ghanbarzadeh and Sanam Arami Copyright © 2013 Saeed Ghanbarzadeh and Sanam Arami. All rights reserved. In Vitro Release Kinetics of Antituberculosis Drugs from Nanoparticles Assessed Using a Modified Dissolution Apparatus Wed, 10 Jul 2013 11:29:10 +0000 The aim of this study was to assess the in vitro release kinetics of antituberculosis drug-loaded nanoparticles (NPs) using a “modified” cylindrical apparatus fitted with a regenerated cellulose membrane attached to a standard dissolution apparatus (modifiedcylinder method). The model drugs that were used were rifampicin (RIF) and moxifloxacin hydrochloride (MX). Gelatin and polybutyl cyanoacrylate (PBCA) NPs were evaluated as the nanocarriers, respectively. The dissolution and release kinetics of the drugs from loaded NPs were studied in different media using the modified cylinder method and dialysis bag technique was used as the control technique. The results showed that use of the modified cylinder method resulted in different release profiles associated with unique release mechanisms for the nanocarrier systems investigated. The modified cylinder method also permitted discrimination between forced and normal in vitro release of the model drugs from gelatin NPs in the presence or absence of enzymatic degradation. The use of dialysis bag technique resulted in an inability to differentiate between the mechanisms of drug release from the NPs in these cases. This approach offers an effective tool to investigate in vitro release of RIF and MX from NPs, which further indicate that this technique can be used for performance testing of nanosized carrier systems. Yuan Gao, Jieyu Zuo, Nadia Bou-Chacra, Terezinha de Jesus Andreoli Pinto, Sophie-Dorothee Clas, Roderick B. Walker, and Raimar Löbenberg Copyright © 2013 Yuan Gao et al. All rights reserved. Novel 4-Arm Poly(Ethylene Glycol)-Block-Poly(Anhydride-Esters) Amphiphilic Copolymer Micelles Loading Curcumin: Preparation, Characterization, and In Vitro Evaluation Mon, 08 Jul 2013 14:14:31 +0000 A novel 4-arm poly(ethylene glycol)-block-poly(anhydride-esters) amphiphilic copolymer (4-arm PEG-b-PAE) was synthesized by esterization of 4-arm poly(ethylene glycol) and poly(anhydride-esters) which was obtained by melt polycondensation of α-, ω-acetic anhydride terminated poly(L-lactic acid). The obtained 4-arm PEG-b-PAE was characterized by 1H-NMR and gel permeation chromatography. The critical micelle concentration of 4-arm PEG-b-PAE was 2.38 μg/mL. The curcumin-loaded 4-arm PEG-b-PAE micelles were prepared by a solid dispersion method and the drug loading content and encapsulation efficiency of the micelles were 7.0% and 85.2%, respectively. The curcumin-loaded micelles were spherical with a hydrodynamic diameter of 151.9 nm. Curcumin was encapsulated within 4-arm PEG-b-PAE micelles amorphously and released from the micelles, faster in pH 5.0 than pH 7.4, presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. The hemolysis rate of the curcumin-loaded 4-arm PEG-b-PAE micelles was 3.18%, which was below 5%. The IC50 value of the curcumin-loaded micelles against Hela cells was 10.21 μg/mL, lower than the one of free curcumin (25.90 μg/mL). The cellular uptake of the curcumin-loaded micelles in Hela cell increased in a time-dependent manner. The curcumin-loaded micelles could induce G2/M phase cell cycle arrest and apoptosis of Hela cells. Li Lv, Yuanyuan Shen, Min Li, Xiaofen Xu, Mingna Li, Shengrong Guo, and Shengtang Huang Copyright © 2013 Li Lv et al. All rights reserved. 1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR-2 Tyrosine Kinase Inhibitors: Synthesis, Biological Evaluation, and Molecular Modelling Studies Sun, 07 Jul 2013 13:31:31 +0000 The vascular endothelial growth factor receptor-2 (VEGFR-2) is a tyrosine kinase receptor involved in the growth and differentiation of endothelial cells that are implicated in tumor-associated angiogenesis. In this study, novel 1-aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas were synthesized and evaluated for the VEGFR-2 tyrosine kinase inhibition. Three of these compounds showed good VEGFR-2 inhibition presenting low IC50 values (150–199 nM) in enzymatic assays, showing also a significant proliferation inhibition of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) at low concentrations (0.5–1 µM), using the Bromodeoxyuridine (BrdU) assay, not affecting cell viability. The determination of the total and phosphorylated (active) VEGFR-2 was performed by western blot, and it was possible to conclude that the compounds significantly inhibit the phosphorylation of the receptor at 1 µM pointing to their antiproliferative mechanism of action in HUVECs. The molecular rationale for inhibiting the tyrosine kinase domain of VEGFR-2 was also performed and discussed using molecular docking studies. Pedro Soares, Raquel Costa, Hugo J. C. Froufe, Ricardo C. Calhelha, Daniela Peixoto, Isabel C. F. R. Ferreira, Rui M. V. Abreu, Raquel Soares, and Maria-João R. P. Queiroz Copyright © 2013 Pedro Soares et al. All rights reserved. Nanocarriers for Diagnosis and Targeting of Breast Cancer Mon, 24 Jun 2013 15:34:55 +0000 Breast cancer nanotherapeutics is consistently progressing and being used to remove the various limitations of conventional method available for the diagnosis and treatment of breast cancer. Nanoparticles provide an interdisciplinary area for research in imaging, diagnosis, and targeting of breast cancer. With advanced physicochemical properties and better bioavailability, they show prolonged blood circulation with efficient tumor targeting. Passive targeting mechanisms by using leaky vasculature, tumor microenvironment, or direct local application and active targeting approaches using receptor antibody, amplification in the ability of nanoparticles to target specific tumor can be achieved. Nanoparticles are able to reduce cytotoxic effect of the active anticancer drugs by increasing cancer cell targeting in comparison to conventional formulations. Various nanoparticles-based formulations are in the preclinical and clinical stages of development; among them, polymeric drug micelles, liposomes, dendrimer, carbon nanotubes, and nanorods are the most common. In this review, we have discussed the role of nanoparticles with respect to oncology, by particularly focusing on the breast cancer and various nanodelivery systems used for targeting action. Arun Sharma, Nitin Jain, and Rashmi Sareen Copyright © 2013 Arun Sharma et al. All rights reserved. Chitosan Combined with Poly-L-arginine as Efficient, Safe, and Serum-Insensitive Vehicle with RNase Protection Ability for siRNA Delivery Sun, 23 Jun 2013 11:44:51 +0000 Chitosan (CS) combined with poly-L-arginine (PLA) was formulated and evaluated for its performance to deliver siRNA to HeLa cells expressing enhanced green fluorescent protein (EGFP). Compared with the formulations using single polymer in which the polyplexes were completely formed at the weight ratio of >20 : 1 for CS/siRNA or 1 : 1 for PLA/siRNA, the combination of CS and PLA could reduce the amounts of the polymers required for the complete complexation with siRNA, thereby forming positively charged, nanosized polyplex at the weight ratio of CS/PLA/siRNA of 5 : 0.5: 1. In addition, while the transfection efficiency of CS/siRNA and PLA/siRNA was very low at physiological pH (7.4), CS/PLA/siRNA at the optimal weight ratio of 5 : 0.5 : 1 satisfactorily silenced the endogenous EGFP gene at pH 7.4 as well as at pH 6.4 without the deterrent effect from serum. The combined polymers could protect siRNA from RNase degradation over a period of at least 6 h. Furthermore, MTT assay results demonstrated that CS/PLA/siRNA complexes showed acceptably low cytotoxicity with 75% cell viability. Therefore, CS combined with PLA is easy to prepare, safe, and promising for use as an efficient siRNA delivery vehicle. Samarwadee Plianwong, Praneet Opanasopit, Tanasait Ngawhirunpat, and Theerasak Rojanarata Copyright © 2013 Samarwadee Plianwong et al. All rights reserved. Improving Drug Loading of Mucosal Solvent Cast Films Using a Combination of Hydrophilic Polymers with Amoxicillin and Paracetamol as Model Drugs Tue, 11 Jun 2013 11:31:15 +0000 Solvent cast mucosal films with improved drug loading have been developed by combining carboxymethyl cellulose (CMC), sodium alginate (SA), and carrageenan (CAR) using paracetamol and amoxicillin as model drugs and glycerol (GLY) as plasticizer. Films were characterized using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), folding resilience, swelling capacity, mucoadhesivity, and drug dissolution studies. SA, CMC, and GLY (5 : 3 : 6) films showed maximum amoxicillin loading of 26.3% whilst CAR, CMC, and GLY (1 : 2 : 3) films had a maximum paracetamol loading of 40%. XRPD analysis showed different physical forms of the drugs depending on the amount loaded. Films containing 29.4% paracetamol and 26.3% amoxicillin showed molecular dispersion of the drugs while excess paracetamol was observed on the film surface when the maximum 40% was loaded. Work of adhesion was similar for blank films with slightly higher cohesiveness for CAR and CMC based films, but the differences were significant between paracetamol and amoxicillin containing films. The stickiness and cohesiveness for drug loaded films were generally similar with no significant differences. The maximum percentage cumulative drug release was 84.65% and 70.59% for paracetamol and amoxicillin, respectively, with anomalous case two transport mechanism involving both drug diffusion and polymer erosion. Joshua Boateng, Justine Mani, and Farnoosh Kianfar Copyright © 2013 Joshua Boateng et al. All rights reserved. Antioxidant and Renoprotective Effects of Spirogyra neglecta (Hassall) Kützing Extract in Experimental Type 2 Diabetic Rats Mon, 03 Jun 2013 15:47:31 +0000 Spirogyra neglecta extract (SNE) has shown antihyperglycemia and antihyperlipidemia in type 2 diabetic mellitus (T2DM) rats. This study investigated the antioxidant and renoprotective effects of SNE in T2DM rats induced by high-fat diet with low-single dose streptozotocin. T2DM rats were fed daily with SNE (0.25, 0.5, and 1 g/kg BW) for 12 weeks. Renal morphology, malondialdehyde levels, qPCR, and western blotting were analyzed. Renal cortical slices were used to determine renal transport of organic anions, which are estrone sulfate and para-aminohippurate, mediated through organic anion transporter 3-Oat3. Insulin and PKC were known to activate Oat3 function while it was inhibited by PKC. Compared to T2DM, plasma glucose, triglyceride, insulin resistance, renal morphology, and malondialdehyde levels were significantly improved by SNE supplementation. Reduced glutathione peroxidase and nuclear factor B expressions were related to antioxidant effect of SNE. Oat3 mRNA and protein were not different among groups, but insulin-stimulated rOat3 followed by anion uptakes was abolished in T2DM. This was restored in the slices from SNE treatment. The mechanism of SNE-improved Oat3 was associated with PKC and PKC expressions and activities. These findings indicate that SNE has beneficial effects on renal transport through antioxidant enzymes and PKCs in T2DM rats. Atcharaporn Ontawong, Naruwan Saowakon, Pornpun Vivithanaporn, Anchalee Pongchaidecha, Narissara Lailerd, Doungporn Amornlerdpison, Anusorn Lungkaphin, and Chutima Srimaroeng Copyright © 2013 Atcharaporn Ontawong et al. All rights reserved. Design Expert Supported Mathematical Optimization and Predictability Study of Buccoadhesive Pharmaceutical Wafers of Loratadine Tue, 28 May 2013 11:51:23 +0000 Objective. The objective of this work encompasses the application of the response surface approach in the development of buccoadhesive pharmaceutical wafers of Loratadine (LOR). Methods. Experiments were performed according to a 32 factorial design to evaluate the effects of buccoadhesive polymer, sodium alginate (), and lactose monohydrate as ingredient, of hydrophilic matrix former () on the bioadhesive force, disintegration time, percent (%) swelling index, and time taken for 70% drug release (). The effect of the two independent variables on the response variables was studied by response surface plots and contour plots generated by the Design-Expert software. The desirability function was used to optimize the response variables. Results. The compatibility between LOR and the wafer excipients was confirmed by differential scanning calorimetry, FTIR spectroscopy, and X-ray diffraction (XRD) analysis. Bioadhesion force, measured with TAXT2i texture analyzer, showed that the wafers had a good bioadhesive property which could be advantageous for retaining the drug into the buccal cavity. Conclusion. The observed responses taken were in agreement with the experimental values, and Loratadine wafers were produced with less experimental trials, and a patient compliant product was achieved with the concept of formulation by design. Prithviraj Chakraborty, Surajit Dey, Versha Parcha, Shiv Sankar Bhattacharya, and Amitava Ghosh Copyright © 2013 Prithviraj Chakraborty et al. All rights reserved. The Conyza triloba Extracts with High Chlorophyll Content and Free Radical Scavenging Activity Had Anticancer Activity in Cell Lines Thu, 23 May 2013 15:06:45 +0000 The discovery of anticancer agents paradigm has been shifted to natural resources to overcome the toxicity of many synthetic agents at early clinical stages. In the present study, the antimutagenic, anticancer, phytochemistry, and free radical scavenging activities of five extracts of Conyza triloba were investigated. Extracts II (water : methanol), III (methylene chloride), and IV (methylene chloride : methanol) had the highest chlorophyll content and the highest superoxide scavenging, and metal chelating activities comparable to that of trolox. They also showed DPPH• scavenging activities better than that of α-tocopherol. Virtually all extracts exerted a strong (>40% reduction) antimutagenic activity against sodium azide and benzopyrene. Extracts II, III, and IV showed a remarkable growth inhibition profile with GI50 of 0.07–0.87 μg for Hepa1c1c7 and H4IIE1, A549, HT29, and PC3 cell lines and totally abated the growth of all cell lines, except for the breast cells, at 0.3–7.0 μg. The present study found a strong correlation between the chlorophyll content of Conyza extracts and their DDPH scavenging, metal chelating, and in vitro cytotoxic and cytostatic activities most probably through triggering apoptosis. This study could offer a platform for future studies and help selecting the vital features that identify the extract with potential anticancer activities. Wael M. El-Sayed, Warda A. Hussin, Ahmed A. Mahmoud, and Mohamed A. AlFredan Copyright © 2013 Wael M. El-Sayed et al. All rights reserved. Hp--CD-Voriconazole In Situ Gelling System for Ocular Drug Delivery: In Vitro, Stability, and Antifungal Activities Assessment Thu, 09 May 2013 08:33:57 +0000 The objective of the present study was to design ophthalmic delivery systems based on polymeric carriers that undergo sol-to-gel transition upon change in temperature or in the presence of cations so as to prolong the effect of HP-β-CD Voriconazole (VCZ) in situ gelling formulations. The in situ gelling formulations of Voriconazole were prepared by using pluronic F-127 (PF-127) or with combination of pluronic F-68 (PF-68) and sodium alginate by cold method technique. The prepared formulations were evaluated for their physical appearance, drug content, gelation temperature (), in vitro permeation studies, rheological properties, mucoadhesion studies, antifungal studies, and stability studies. All batches of in situ formulations had satisfactory pH ranging from 6.8 to 7.4, drug content between 95% and 100%, showing uniform distribution of drug. As the concentration of each polymeric component was increased, that is, PF-68 and sodium alginate, there was a decrease in with increase in viscosity and mucoadhesive strength. The in vitro drug release decreased with increase in polymeric concentrations. The stability data concluded that all formulations showed the low degradation and maximum shelf life of 2 years. The antifungal efficiency of the selected formulation against Candida albicans and Asperigillus fumigatus confirmed that designed formulation has prolonged effect and retained its properties against fungal infection. Pravin Pawar, Heena Kashyap, Sakshi Malhotra, and Rakesh Sindhu Copyright © 2013 Pravin Pawar et al. All rights reserved. Preparation of Biocompatible Carboxymethyl Chitosan Nanoparticles for Delivery of Antibiotic Drug Mon, 18 Mar 2013 09:34:21 +0000 Objective. To prepare biocompatible ciprofloxacin-loaded carboxymethyl chitosan nanoparticles (CCC NPs) and evaluate their cell specificity as well as antibacterial activity against Escherichia coli in vitro. Methods. CCC NPs were prepared by ionic cross-linking method and optimized by using Box-Behnken response surface method (BBRSM). Zeta potential, drug encapsulation, and release of the obtained nanoparticles in vitro were thoroughly investigated. Minimum inhibitory concentration (MIC) and killing profiles of free or ciprofloxacin-loaded nanoparticles against Escherichia coli were documented. The cytotoicity of blank nanoparticles and cellular uptake of CCC NPs were also investigated. Results. The obtained particles were monodisperse nanospheres with an average hydrated diameter of 151 ± 5.67 nm and surface of charge −22.9 ± 2.21 mV. The MICs of free ciprofloxacin and CCC NPs were 0.16 and 0.08 g/mL, respectively. Blank nanoparticles showed no obvious cell inhibition within 24 h, and noticeable phagocytosis effect was observed in the presence of CCC NPs. Conclusion. This study shows that CCC NPs have stronger antibacterial activity against Escherichia coli than the free ciprofloxacin because they can easily be uptaken by cells. The obtained CCC NPs have promising prospect in drug delivery field. Liang Zhao, Bingya Zhu, Yunhong Jia, Wenjiu Hou, and Chang Su Copyright © 2013 Liang Zhao et al. All rights reserved. The Improvement of The Endogenous Antioxidant Property of Stone Fish (Actinopyga lecanora) Tissue Using Enzymatic Proteolysis Sun, 17 Mar 2013 14:20:22 +0000 The stone fish (Actinopyga lecanora) ethanolic and methanolic tissue extracts were investigated for total phenolic contents (TPCs) as well as antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging activity and ferric reducing antioxidant power (FRAP) assays. Both extracts showed low amount of phenolics (20.33 to 17.03 mg of gallic acid equivalents/100 g dried sample) and moderate antioxidant activity (39% to 34%  DPPH• radical scavenging activity and 23.95 to 22.30 mmol/100 mL FeSO4 FRAP value). Enzymatic proteolysis was carried out in order to improve the antioxidant activity using six commercially available proteases under their optimum conditions. The results revealed that the highest increase in antioxidant activity up to 85% was obtained for papain-generated proteolysate, followed by alcalase (77%), trypsin (75%), pepsin (68%), bromelain (68%), and flavourzyme (50%) as measured by DPPH• radical scavenging activity, whilst for the FRAP value, the highest increase in the antioxidant activity up to 39.2 mmol/100 mL FeSO4 was obtained for alcalase-generated proteolysate, followed by papain (29.5 mmol/100 mL FeSO4), trypsin (23.2 mmol/100 mL FeSO4), flavourzyme (24.7 mmol/100 mL FeSO4), bromelain (22.9 mmol/100 mL FeSO4), and pepsin (20.8 mmol/100 mL FeSO4). It is obvious that proteolysis of stone fish tissue by proteolytic enzymes can considerably enhance its antioxidant activity. Sara Bordbar, Afshin Ebrahimpour, Azizah Abdul Hamid, Mohd Yazid Abdul Manap, Farooq Anwar, and Nazamid Saari Copyright © 2013 Sara Bordbar et al. All rights reserved. Structure and Antimicrobial Properties of Monensin A and Its Derivatives: Summary of the Achievements Wed, 13 Feb 2013 15:00:00 +0000 In this paper structural and microbiological studies on the ionophorous antibiotic monensin A and its derivatives have been collected. Monensin A is an ionophore which selectively complexes and transports sodium cation across lipid membranes, and therefore it shows a variety of biological properties. This antibiotic is commonly used as coccidiostat and nonhormonal growth promoter. The paper focuses on both the latest and earlier achievements concerning monensin A antimicrobial activity. The activities of monensin derivatives, including modifications of hydroxyl groups and carboxyl group, are also presented. Daniel Łowicki and Adam Huczyński Copyright © 2013 Daniel Łowicki and Adam Huczyński. All rights reserved. Antioxidant Capacity and the Correlation with Major Phenolic Compounds, Anthocyanin, and Tocopherol Content in Various Extracts from the Wild Edible Boletus edulis Mushroom Sun, 30 Dec 2012 09:16:56 +0000 Boletus edulis is a wild edible mushroom habitually consumed by rural populations. Ethanolic and methanolic extracts was obtained in cold and hot water from dried fruit bodies. The antioxidant activity of freeze-dried extracts from B. edulis were investigated using free radicals scavenging activity, reducing power, metal chelating effect, inhibition of lipid peroxidation, and the identification of antioxidant compounds. The levels of different compounds with antioxidant properties were higher in alcoholic extracts compared with aqueous extracts. Rosmarinic acid was the major phenolic compound, it being identified in a concentration between and  mg/100 g extract. A positive correlation between the content of total phenols, flavonoids, anthocyanins, and tocopherols, and the antioxidant capacity of the extracts was determined. The results showed that the ethanolic extract of Romanian wild mushroom B. edulis represents a natural source of functional compounds. Emanuel Vamanu and Sultana Nita Copyright © 2013 Emanuel Vamanu and Sultana Nita. All rights reserved. Bioequivalence and Population Pharmacokinetic Modeling of Two Forms of Antibiotic, Cefuroxime Lysine and Cefuroxime Sodium, after Intravenous Infusion in Beagle Dogs Sun, 15 Jul 2012 14:11:06 +0000 To investigate the bioequivalence and the population pharmacokinetics of cefuroxime lysine and cefuroxime sodium in healthy beagle dogs. A randomized 2-period crossover design in 18 healthy beagle dogs after receiving 20, 40, and 80 mg/kg of cefuroxime lysine or cefuroxime sodium was conducted. A 3-compartment open model was used as the basic model for the population pharmacokinetic study. Both of the antibiotics exhibited dose-proportional pharmacokinetics over the dose range of 20–80 mg/kg. The mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium was 1.05 (range, 0.71 to 1.42), with a significant difference between males and females. The estimates of population pharmacokinetic of CL, V1, Q2, V2, Q3, V3 were 3.74 mL/h, 1.70 mL, 29.5 mL/min, 3.58 mL, 0.31 mL/min, and 158 mL for cefuroxime lysine and 4.10 mL/h, 1.00 mL, 38.5 mL/min, 4.19 mL, 0.06 mL/min, and 13.6 mL for cefuroxime sodium, respectively. The inter-individual variability was determined to be less than 29.1%. A linear pharmacokinetic was revealed for cefuroxime lysine and cefuroxime sodium in dogs after intravenous infusion, and the bioequivalence of these forms of the antibiotic was observed with the significant gender-related differences in mean relative bioavailability of cefuroxime lysine versus cefuroxime sodium. Longshan Zhao, Qing Li, Xingang Li, Ran Yin, Xiaohui Chen, Lulu Geng, and Kaishun Bi Copyright © 2012 Longshan Zhao et al. All rights reserved. Therapeutic Strategies Based on Polymeric Microparticles Wed, 16 May 2012 08:21:12 +0000 The development of the field of materials science, the ability to perform multidisciplinary scientific work, and the need for novel administration technologies that maximize therapeutic effects and minimize adverse reactions to readily available drugs have led to the development of delivery systems based on microencapsulation, which has taken one step closer to the target of personalized medicine. Drug delivery systems based on polymeric microparticles are generating a strong impact on preclinical and clinical drug development and have reached a broad development in different fields supporting a critical role in the near future of medical practice. This paper presents the foundations of polymeric microparticles based on their formulation, mechanisms of drug release and some of their innovative therapeutic strategies to board multiple diseases. C. Vilos and L. A. Velasquez Copyright © 2012 C. Vilos and L. A. Velasquez. All rights reserved. Antinociceptive Activity of the Chloroform Fraction of Dioclea virgata (Rich.) Amshoff (Fabaceae) in Mice Tue, 05 Jul 2011 08:26:41 +0000 Acute treatment with the chloroform fraction of Dioclea virgata (Rich.) Amshoff (CFDv) in mice produced decreased ambulation and sedation in the behavioral pharmacological screening. Doses of 125 and 250 mg/kg CFDv decreased latency of sleep onset in the test of sleeping time potentiation. In the open field, animals treated with CFDv reduced ambulation and rearing (250 mg/kg), as well as defecation (125; 250 mg/kg). Regarding the antinociceptive activity, CFDv (125, 250, 500 mg/kg) increased latency to first writhing and decreased the number of writhings induced by acetic acid. In the formalin test, CFDv (250 mg/kg) decreased paw licking time in the first and second phases indicating antinociceptive activity that can be mediated both peripherally and at the central level. CFDv did not affect motor coordination until 120 minutes after treatment. CFDv shows psychopharmacological effects suggestive of CNS-depressant drugs with promising antinociceptive activity. Vanine Gomes Mota, Fabíola Lélis de Carvalho, Liana Clébia Soares Lima de Morais, Jnanabrata Bhattacharyya, Reinaldo Nóbrega de Almeida, and Jacicarlos Lima de Alencar Copyright © 2011 Vanine Gomes Mota et al. All rights reserved. Mechanisms of Resistance to EGFR TKIs and Development of a New Generation of Drugs in Non-Small-Cell Lung Cancer Thu, 02 Jun 2011 18:41:48 +0000 Gefitinib and erlotinib, which are epidermal growth factor receptor- (EGFR-) specific tyrosine kinase inhibitors (TKIs), are widely used as molecularly targeted drugs for non-small-cell lung cancer (NSCLC). Currently, the search for EGFR gene mutations is becoming essential for the treatment of NSCLC since these have been identified as predictive factors for drug sensitivity. On the other hand, in almost all patients responsive to EGFR-TKIs, acquired resistance is a major clinical problem. Mechanisms of acquired resistance reported in the past few years include secondary mutation of the EGFR gene, amplification of the MET gene, and overexpression of HGF; novel pharmaceutical agents are currently being developed to overcome resistance. This review focuses on these mechanisms of acquired resistance to EGFR-TKIs and discusses how they can be overcome. Takayuki Kosaka, Ei Yamaki, Akira Mogi, and Hiroyuki Kuwano Copyright © 2011 Takayuki Kosaka et al. All rights reserved. Bioactivity Determination of Native and Variant Forms of Therapeutic Interferons Thu, 03 Mar 2011 18:14:09 +0000 The traditional antiviral assays for the determination of interferon potency are reported to have considerable variability between and within assays. Although several reporter gene assays based on interferon-inducible promoter activities have been reported, data from comprehensive validation studies are lacking and few studies have been conducted to analyze the variant forms of interferons, which could have undesirable clinical implications. Here, a reporter gene assay employing a HEK293 cell line stably transfected with luciferase gene under the control of interferon-stimulated response element promoter was developed and validated. The assay was found to be more sensitive, with a larger detection range than the antiviral assay. Several cytokines tested did not interfere with the test, suggesting the assay possesses a certain degree of selectivity. Moreover, the robustness of the assay was demonstrated by minimal variations in the results generated by different analysts and cell passage number (up to 52 passages). Finally, the method was employed to analyze several interferon variants (interferon- 2a) and we found that the aggregated form has completely lost its potency; while a modest loss of bioactivity in oxidized interferon was observed (approx. 23%), the deamidated form essentially retained its activity. Louise Larocque, Alex Bliu, Ranran Xu, Abebaw Diress, Junzhi Wang, Rongtuan Lin, Runtao He, Michel Girard, and Xuguang Li Copyright © 2011 Louise Larocque et al. All rights reserved. Separation and Purification of Two Flavone Glucuronides from Erigeron multiradiatus (Lindl.) Benth with Macroporous Resins Wed, 11 Nov 2009 11:15:06 +0000 Scutellarein-7---D-glucuronide (SG) and apigenin-7---D-glucuronide (AG) are two major bioactive constituents in Erigeron multiradiatus. In this study, a simple method for preparative separation of the two flavone glucuronides was established with macroporous resins. The performance and adsorption characteristics of eight macroporous resins including AB-8, HPD100, HPD450, HPD600, D100, D101, D141 and D160 had been evaluated. The results confirmed that D141 resin was preferred choice, which offered the best adsorption and desorption capacities for the two glucuronides among the tested resins. Sorption isotherms were constructed for D141 resin and fitted well to the Freundlich and Langmuir models (). After one run treatment with D141 resin, the two constituents' content was increased from 2.14% and 1.34% in the crude extract of E. multiradiatus to 24.63% and 18.42% in the final products with the recoveries of 82.5% and 85.4%, respectively. The enrichment of SG and AG can be easily and effectively achieved via adsorption and desorption on D141 resin, and the method can be referenced for large-scale separation and purification of flavone glucuronides from herbal raw materials. Zhi-feng Zhang, Yuan Liu, Pei Luo, and Hao Zhang Copyright © 2009 Zhi-feng Zhang et al. All rights reserved. Poly(hydroxyalkanoates)-Based Polymeric Nanoparticles for Drug Delivery Thu, 17 Sep 2009 14:22:39 +0000 Poly (hydroxyalkanoates) (PHAs) have recently attracted a great deal of academic and industrial interest for their biodegradability and biocompatibility making them suitable for environmental and biomedical applications. Poly(3-hydroxybutyrate-) (PHB-) and Poly(DL-lactide-co-glycolide) (PLGA-) based nanoparticles were prepared using the dialysis method as yet unreported for the preparation of nanoparticles based on PHB. Processing conditions were varied in order to evaluate their influence on morphology, drug encapsulation, and size of nanoparticles. The relevant results obtained give a theoretical understanding of the phenomenon occurring during colloidal formation. The adopted procedure allows for a relatively small diameter and homogeneity in size distribution of the PHB nanoparticles to be obtained compared to other methods like the one based on solvent evaporation which leads to particles on microscale. The biocompatibility of PHB and relative nanoparticles was investigated and both exhibited very good cytocompatibility. Cesare Errico, Cristina Bartoli, Federica Chiellini, and Emo Chiellini Copyright © 2009 Cesare Errico et al. All rights reserved.