Journal of Drug Delivery The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Preparation and Characterization of Liquisolid Compacts for Improved Dissolution of Telmisartan Sun, 12 Oct 2014 10:47:49 +0000 The objective of the present work was to obtain pH independent and improved dissolution profile for a poorly soluble drug, telmisartan using liquisolid compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle, Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations were evaluated for drug excipient interactions, change in crystallinity of drug, flow properties, and general quality control tests of tablets using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), angle of repose, and various pharmacopoeial tests. In vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and 7.4). Stability studies were performed at 40°C and 75% RH for three months. The formulation was found to comply with Indian pharmacopoeial limits for tablets. FTIR studies confirmed no interaction between drug and excipients. XRD and DSC studies indicate change/reduction in crystallinity of drug. Dissolution media were selected based on the solubility studies. The optimized formulation showed pH independent release profile with significant improvement in dissolution compared to plain drug and conventional marketed formulation. No significant difference was seen in the tablet properties, and drug release profile after storage for 3 months. Naveen Chella, Nataraj Narra, and Tadikonda Rama Rao Copyright © 2014 Naveen Chella et al. All rights reserved. The Signature Sequence Region of the Human Drug Transporter Organic Anion Transporting Polypeptide 1B1 Is Important for Protein Surface Expression Thu, 09 Oct 2014 13:47:24 +0000 The organic anion transporting polypeptides (OATPs) encompass a family of membrane transport proteins responsible for the uptake of xenobiotic compounds. Human organic anion transporting polypeptide 1B1 (OATP1B1) mediates the uptake of clinically relevant compounds such as statins and chemotherapeutic agents into hepatocytes, playing an important role in drug delivery and detoxification. The OATPs have a putative 12-transmembrane domain topology and a highly conserved signature sequence (human OATP1B1: DSRWVGAWWLNFL), spanning the extracellular loop 3/TM6 boundary. The presence of three conserved tryptophan residues at the TM interface suggests a structural role for the sequence. This was investigated by site-directed mutagenesis of selected amino acids within the sequence D251E, W254F, W258/259F, and N261A. Transport was measured using the substrate estrone-3-sulfate and surface expression detected by luminometry and confocal microscopy, facilitated by an extracellular FLAG epitope. Uptake of estrone-3-sulfate and the surface expression of D251E, W254F, and W258/259F were both significantly reduced from the wild type OATP1B1-FLAG in transfected HEK293T cells. Confocal microscopy revealed that protein was produced but was retained intracellularly. The uptake and expression of N261A were not significantly different. The reduction in surface expression and intracellular protein retention indicates a structural and/or membrane localization role for these signature sequence residues in the human drug transporter OATP1B1. Jennina Taylor-Wells and David Meredith Copyright © 2014 Jennina Taylor-Wells and David Meredith. All rights reserved. Design Optimization and In Vitro-In Vivo Evaluation of Orally Dissolving Strips of Clobazam Sun, 28 Sep 2014 00:00:00 +0000 Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24 sec), TS (2.85 N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of (95.87%), (71.42%), (98.125%), and (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles. Rajni Bala, Sushil Khanna, and Pravin Pawar Copyright © 2014 Rajni Bala et al. All rights reserved. Development of Corn Starch-Neusilin UFL2 Conjugate as Tablet Superdisintegrant: Formulation and Evaluation of Fast Disintegrating Tablets Tue, 23 Sep 2014 05:46:23 +0000 In the present study, corn Starch-Neusilin UFL2 conjugates were prepared by physical, chemical, and microwave methods with the aim of using the conjugates as tablet superdisintegrant. Various powder tests, namely, angle of repose, bulk density, tapped density, Hausner’s ratio, Carr’s index, swelling index, and powder porosity were conducted on the samples. The conjugates were characterized by ATR-FTIR, XRD, DSC, and SEM techniques. Heckel and Kawakita models were applied to carry out compression studies for the prepared conjugates. Fast disintegrating tablets of domperidone were prepared using corn starch and corn Starch-Neusilin UFL2 conjugates as tablet superdisintegrants in different concentrations. Conjugates were found to possess good powder flow and tabletting properties. Heckel analysis indicated that the conjugates prepared by microwave method showed the slowest onset of plastic deformation while Kawakita analysis indicated that the conjugates prepared by microwave method exhibited the highest amount of total plastic deformation. The study revealed that the corn Starch-Neusilin UFL2 conjugates possess improved powder flow properties and could be a promising superdisintegrant for preparing fast disintegrating tablet. Also, the results sugessted that the microwave method was found to be most effective for the preparation of corn Starch-Neusilin UFL2 conjugates. Prateek Juneja, Birender Kaur, Oluwatoyin A. Odeku, and Inderbir Singh Copyright © 2014 Prateek Juneja et al. All rights reserved. Application of Experimental Design in Preparation of Nanoliposomes Containing Hyaluronidase Tue, 09 Sep 2014 08:02:43 +0000 Hyaluronidase is an enzyme that catalyzes breakdown of hyaluronic acid. This property is utilized for hypodermoclysis and for treating extravasation injury. Hyaluronidase is further studied for possible application as an adjuvant for increasing the efficacy of other drugs. Development of suitable carrier system for hyaluronidase would help in coadministration of other drugs. In the present study, the hyaluronidase was encapsulated in liposomes. The effect of variables, namely, phosphatidylcholine (PC), cholesterol, temperature during film formation (T1), and speed of rotation of the flask during film formation (SPR) on percentage of protein encapsulation, was first analyzed using factorial design. The study showed that level of phosphatidylcholine had the maximum effect on the outcome. The effect of interaction of PC and SPR required for preparation of nanoliposomes was identified by central composite design (CCD). The dependent variables were percentage protein encapsulation, particle size, and zeta potential. The study showed that ideal conditions for production of hyaluronidase loaded nanoliposomes are PC—140 mg and cholesterol 1/5th of PC when the SPR is 150 rpm and T1 is 50°C. Narayanan Kasinathan, Subrahmanyam​ Mallikarjuna Volety​, and Venkata Rao Josyula​ Copyright © 2014 Narayanan Kasinathan et al. All rights reserved. Hydroxypropyl-β-cyclodextrin: A Novel Transungual Permeation Enhancer for Development of Topical Drug Delivery System for Onychomycosis Wed, 06 Aug 2014 07:24:38 +0000 The treatment of onychomycosis is a challenging task because of unique barrier properties of the nail plate which hampers the passage of antifungal drugs in a concentration required to eradicate the deeply seated causative fungi in the nail bed. In present investigation, application of hydroxypropyl-β-cyclodextrin (HP-β-CD) was established as an effective and nail friendly transungual drug permeation enhancer especially for poorly water soluble drugs using terbinafine hydrochloride as a poorly soluble drug. HP-β-CD significantly improves hydration of nail plates and increases solubility of terbinafine hydrochloride in the aqueous environment available therein, which leads to uninterrupted drug permeation through water filled pores of hydrogel-like structure of hydrated nail plates. A nail lacquer formulation was designed with an objective to deliver the drug in an effective concentration across nail plates, using HP-β-CD as a permeation enhancer. The formulations containing HP-β-CD showed higher flux than the control formulation in in vitro drug permeation study. The formulation containing 10% w/v of HP-β-CD showed maximum flux of  μg/mL/cm2 as compared to the control flux of  μg/mL/cm2. This finding supports application of HP-β-CD as an effective permeation enhancer for transungual delivery of terbinafine hydrochloride and possibly other poorly water soluble drugs where HP-β-CD can act as a solubilizer. Pradeep Chouhan and T. R. Saini Copyright © 2014 Pradeep Chouhan and T. R. Saini. All rights reserved. Tailor-Made Pentablock Copolymer Based Formulation for Sustained Ocular Delivery of Protein Therapeutics Sun, 22 Jun 2014 06:08:27 +0000 The objective of this research article is to report the synthesis and evaluation of novel pentablock copolymers for controlled delivery of macromolecules in the treatment of posterior segment diseases. Novel biodegradable PB copolymers were synthesized by sequential ring-opening polymerization. Various ratios and molecular weights of each block (polyglycolic acid, polyethylene glycol, polylactic acid, and polycaprolactone) were selected for synthesis and to optimize release profile of FITC-BSA, IgG, and bevacizumab from nanoparticles (NPs) and thermosensitive gel. NPs were characterized for particle size, polydispersity, entrapment efficiency, and drug loading. In vitro release study of proteins from NPs alone and composite formulation (NPs suspended in thermosensitive gel) was performed. Composite formulations demonstrated no or negligible burst release with continuous near zero-order release in contrast to NPs alone. Hydrodynamic diameter of protein therapeutics and hydrophobicity of PB copolymer exhibited significant effect on entrapment efficiency and in vitro release profile. CD spectroscopy confirmed retention of structural conformation of released protein. Biological activity of released bevacizumab was confirmed by in vitro cell proliferation and cell migration assays. It can be concluded that novel PB polymers can serve a platform for sustained delivery of therapeutic proteins. Sulabh P. Patel, Ravi Vaishya, Gyan Prakash Mishra, Viral Tamboli, Dhananjay Pal, and Ashim K. Mitra Copyright © 2014 Sulabh P. Patel et al. All rights reserved. Mucoadhesive Hydrogel Films of Econazole Nitrate: Formulation and Optimization Using Factorial Design Tue, 10 Jun 2014 05:14:15 +0000 The mucoadhesive hydrogel film was prepared and optimized for the purpose of local drug delivery to oral cavity for the treatment of oral Candidiasis. The mucoadhesive hydrogel film was prepared with the poly(vinyl alcohol) by freeze/thaw crosslinking technique. 32 full factorial design was employed to optimize the formulation. Number of freeze/thaw cycles (4, 6, and 8 cycles) and the concentration of the poly(vinyl alcohol) (10, 15, and 20%) were used as the independent variables whereas time required for 50% drug release, cumulative percent of drug release at 8th hour, and “” of zero order equation were used as the dependent variables. The films were evaluated for mucoadhesive strength, in vitro residence time, swelling study, in vitro drug release, and effectiveness against Candida albicans. The concentration of poly(vinyl alcohol) and the number of freeze/thaw cycles both decrease the drug release rate. Mucoadhesive hydrogel film with 15% poly(vinyl alcohol) and 7 freeze/thaw cycles was optimized. The optimized batch exhibited the sustained release of drug and the antifungal studies revealed that the drug released from the film could inhibit the growth of Candida albicans for 12 hours. Balaram Gajra, Saurabh S. Pandya, Sanjay Singh, and Haribhai A. Rabari Copyright © 2014 Balaram Gajra et al. All rights reserved. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems Wed, 14 May 2014 09:19:28 +0000 Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs. Alka Lohani, Garima Singh, Shiv Sankar Bhattacharya, and Anurag Verma Copyright © 2014 Alka Lohani et al. All rights reserved. Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by 1H-, 2H-, 31P-NMR and Electron Spin Resonance Mon, 05 May 2014 11:15:00 +0000 The properties of an amorphous solid dispersion of cyclosporine A (ASD) prepared with the copolymer alpha cyclodextrin (POLYA) and cyclosporine A (CYSP) were investigated by 1H-NMR in solution and its membrane interactions were studied by 1H-NMR in small unilamellar vesicles and by 31P 2H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine) in comparison with those of POLYA and CYSP alone. 1H-NMR chemical shift variations showed that CYSP really interacts with POLYA, with possible adduct formation, dispersion in the solid matrix of the POLYA, and also complex formation. A coarse approach to the latter mechanism was tested using the continuous variations method, indicating an apparent 1 : 1 stoichiometry. Calculations gave an apparent association constant of log Ka = 4.5. A study of the interactions with phospholipidic dispersions of DMPC showed that only limited interactions occurred at the polar head group level (31P). Conversely, by comparison with the expected chain rigidification induced by CYSP, POLYA induced an increase in the fluidity of the layer while ASD formation led to these effects almost being overcome at 298 K. At higher temperature, while the effect of CYSP seems to vanish, a resulting global increase in chain fluidity was found in the presence of ASD. Jean-Claude Debouzy, David Crouzier, Fréderic Bourbon, Malika Lahiani-Skiba, and Mohamed Skiba Copyright © 2014 Jean-Claude Debouzy et al. All rights reserved. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells Thu, 24 Apr 2014 08:19:00 +0000 During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. Vaibhav Rastogi, Pragya Yadav, Shiv Sankar Bhattacharya, Arun Kumar Mishra, Navneet Verma, Anurag Verma, and Jayanta Kumar Pandit Copyright © 2014 Vaibhav Rastogi et al. All rights reserved. Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells Thu, 24 Apr 2014 07:28:27 +0000 The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma. Parviz Mohammadi Ghalaei, Jaleh Varshosaz, and Hojatollah Sadeghi Aliabadi Copyright © 2014 Parviz Mohammadi Ghalaei et al. All rights reserved. Antibiotic Conjugated Fluorescent Carbon Dots as a Theranostic Agent for Controlled Drug Release, Bioimaging, and Enhanced Antimicrobial Activity Tue, 18 Mar 2014 07:38:35 +0000 A novel report on microwave assisted synthesis of bright carbon dots (C-dots) using gum arabic (GA) and its use as molecular vehicle to ferry ciprofloxacin hydrochloride, a broad spectrum antibiotic, is reported in the present work. Density gradient centrifugation (DGC) was used to separate different types of C-dots. After careful analysis of the fractions obtained after centrifugation, ciprofloxacin was attached to synthesize ciprofloxacin conjugated with C-dots (Cipro@C-dots conjugate). Release of ciprofloxacin was found to be extremely regulated under physiological conditions. Cipro@C-dots were found to be biocompatible on Vero cells as compared to free ciprofloxacin (1.2 mM) even at very high concentrations. Bare C-dots (∼13 mg mL−1) were used for microbial imaging of the simplest eukaryotic model—Saccharomyces cerevisiae (yeast). Bright green fluorescent was obtained when live imaging was performed to view yeast cells under fluorescent microscope suggesting C-dots incorporation inside the cells. Cipro@C-dots conjugate also showed enhanced antimicrobial activity against both model gram positive and gram negative microorganisms. Thus, the Cipro@C-dots conjugate paves not only a way for bioimaging but also an efficient new nanocarrier for controlled drug release with high antimicrobial activity, thereby serving potential tool for theranostics. Mukeshchand Thakur, Sunil Pandey, Ashmi Mewada, Vaibhav Patil, Monika Khade, Ekta Goshi, and Madhuri Sharon Copyright © 2014 Mukeshchand Thakur et al. All rights reserved. Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen Tue, 11 Feb 2014 00:00:00 +0000 The objective of the present work was to develop a metered dose transdermal spray (MDTS) formulation for transdermal delivery of dexketoprofen (DE). DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE) content was developed incorporating 7% (w/w, %) DE, 7% (v/v, %) isopropyl myristate (IPM), and 93% (v/v, %) ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE. Wangding Lu, Huafei Luo, Zhuangzhi Zhu, Yubo Wu, Jing Luo, and Hao Wang Copyright © 2014 Wangding Lu et al. All rights reserved. Polypeptide Multilayer Self-Assembly Studied by Ellipsometry Mon, 10 Feb 2014 13:42:52 +0000 A polypeptide nanofilm made by layer-by-layer (LbL) self-assembly was built on a surface that mimics nonwoven, a material commonly used in wound dressings. Poly-L-lysine (PLL) and poly-L-glutamic acid (PLGA) are the building blocks of the nanofilm, which is intended as an enzymatically degradable lid for release of bactericides to chronic wounds. Chronic wounds often carry infection originating from bacteria such as Staphylococcus aureus and a release system triggered by the degree of infection is of interest. The dry nanofilm was studied with ellipsometry. The thickness of the nanofilm was 60% less in its dry state than in its wet state. The measurements showed that a primer was not necessary to build a stable nanofilm, which is practically important in our case because a nondegradable primer is highly unwanted in a wound care dressing. Added V8 (glutamyl endopeptidase) enzymes only showed adsorption on the nanofilm at room temperature, indicating that the PLL/PLGA “lid” may remain intact until the dressing has been filled with wound exudate at the elevated temperature typical of that of the wound. Marina Craig, Krister Holmberg, Eric Le Ru, and Pablo Etchegoin Copyright © 2014 Marina Craig et al. All rights reserved. Development of Risperidone PLGA Microspheres Tue, 28 Jan 2014 06:41:58 +0000 The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50 : 50 and 75 : 25) were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40 mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50 : 50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75 : 25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug. Susan D’Souza, Jabar A. Faraj, Stefano Giovagnoli, and Patrick P. DeLuca Copyright © 2014 Susan D’Souza et al. All rights reserved. Intravital Microscopic Research of Microembolization with Degradable Starch Microspheres Wed, 13 Nov 2013 11:05:26 +0000 Treatment efficacy in cancer patients using systemically applied cytostatic drugs is decreased by cytotoxic side effects, which limits the use of efficient dosages. Degradable starch microspheres (DSM) are used to apply drugs into blood vessels which supply the target organ leading to drug accumulation in the target organ by reduction of the blood flow. The present investigations show that DSM is a very effective embolization material leading to effective and enhanced accumulation of 5-FU within the liver tumor tissue of experimental induced liver cancer in rats. By using intravital microscopy, a rapid deceleration of the blood flow into the target organ is observed immediately after application of DSM. The microspheres are stepwise degraded in the direction of the systemic blood flow and are totally dissolved after 25 minutes. These stepwise processes leave the degraded material during the degradation process within the vessels leading to temporally reciprocal blood flow via some of the side-arms of the major blood vessels. By using DMS in transarterial chemoembolization (TACE), severe adverse side effects like postembolization syndrome are rarely observed when compared to other embolization materials. The complete degradation of DSM causes only a short-lasting temporary vascular occlusion, which allows a repeat application of DSM in TACE. Micaela Ebert, Juergen Ebert, and Gerd Berger Copyright © 2013 Micaela Ebert et al. All rights reserved. Novel Oncology Therapeutics: Targeted Drug Delivery for Cancer Tue, 22 Oct 2013 10:29:46 +0000 Andreas G. Tzakos, Evangelos Briasoulis, Theresia Thalhammer, Walter Jäger, and Vasso Apostolopoulos Copyright © 2013 Andreas G. Tzakos et al. All rights reserved. Formulation and Evaluation of Liquisolid Compacts for Olmesartan Medoxomil Mon, 21 Oct 2013 16:03:58 +0000 Olmesartan medoxomil is an angiotensin type II receptor blocker, antihypertensive agent, administered orally. It is highly lipophilic (log P 5.5) and a poorly water-soluble drug with absolute bioavailability of 26%. The poor dissolution rate of water-insoluble drugs is still a major problem confronting the pharmaceutical industry. The objective of the present investigation was to develop liquisolid compacts for olmesartan medoxomil to improve the dissolution rate. Liquisolid compacts were prepared using Acrysol El 135 as a solvent, Avicel PH 102, Fujicalin and Neusilin as carrier materials, and Aerosil as coating material in different ratios. The interaction between drug and excipients was characterized by DSC and FT-IR studies, which showed that there is no interaction between drug and excipients. The powder characteristics were evaluated by different flow parameters to comply with pharmacopoeial limits. The dissolution studies for liquisolid compacts and conventional formulations were carried out, and it was found that liquisolid compacts with 80% w/w of Acrysol EL 135 to the drug showed significant higher drug release rates than conventional tablets. Amongst carriers used Fujicalin and Neusilin were found to be more effective carrier materials for liquid adsorption. Shailesh T. Prajapati, Hitesh H. Bulchandani, Dashrath M. Patel, Suresh K. Dumaniya, and Chhaganbhai N. Patel Copyright © 2013 Shailesh T. Prajapati et al. All rights reserved. Simulation of Drug Release from PLGA Particles In Vivo Thu, 10 Oct 2013 15:56:23 +0000 Specific targeting of tissues and/or cells is essential for any type of drug delivery system because this determines the efficacy and side effects of the drug. Poly lactic-co-glycolic acids (PLGA) have long been used as biomaterials for drug delivery due to their excellent biocompatibility and biodegradability. Direct visualization of PLGA particles is feasible even within tissues, and cell specificity of the drug delivery system is normally assessed by using labeled particles. However, particle labeling alone does not address factors such as the release and distribution of the drug. Thus, it is desirable to set up a simulation system of drug release and distribution in vivo. In the present study, we aimed to establish a method to simulate drug distribution in PLGA drug delivery by using Hoechst 33342 as an imitating drug. Our approach enabled us to identify, isolate, and characterize cells exposed to Hoechst 33342 and to deduce the concentration of this fluorescent dye around both targeted and nontargeted cells. We believe that the method described herein will provide essential information regarding the specificity of cell targeting in any type of PLGA drug delivery system. Kaori Sasaki, Martha Igarashi, Manami Hinata, Yuna Komori, and Kouhei Fukushima Copyright © 2013 Kaori Sasaki et al. All rights reserved. Development of Dorzolamide Loaded 6-O-Carboxymethyl Chitosan Nanoparticles for Open Angle Glaucoma Thu, 10 Oct 2013 11:06:50 +0000 Chitosan (CS) is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS) derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs) loaded with dorzolamide hydrochloride (DRZ). CS was reacted with monochloroacetic acid (MCA) for OCM-CS synthesis and was characterized by FT-IR, DSC, and 13C NMR. CS and OCM-CS NPs were prepared by ionic gelation method. Ocular irritation potential were evaluated and therapeutic efficacy was measured by reduction in intraocular pressure (IOP) in normotensive rabbits. Maximum yield was obtained when the ratio of water/isopropyl alcohol was 1/4 at 55°C. The FT-IR, DSC and 13C NMR confirmed the formation of an ether linkage between hydroxyl groups of CS and MCA. The particle size and zeta potential of optimised CSNPs was 250.3 ± 2.62 nm and +33.47 ± 0.723 mV, whereas those for OCM-CSNPs were 187.1 ± 2.72 nm and 30.87 ± 0.86 mV. The entrapment efficiency was significantly improved for OCM-CSNPs, compared to CSNPs. OCM-CSNPs had tailored drug release and improved bioavailability with reduction in pulse entry as compared to CSNPs. Hence, it can be concluded that DRZ loaded OCM-CSNPs would be better alternative option to available eye drops for glaucoma treatment. Ujwala Shinde, Mohammed Hadi Ahmed, and Kavita Singh Copyright © 2013 Ujwala Shinde et al. All rights reserved. Targeting Antigens to Dendritic Cell Receptors for Vaccine Development Tue, 08 Oct 2013 09:26:56 +0000 Dendritic cells (DCs) are highly specialized antigen presenting cells of the immune system which play a key role in regulating immune responses. Depending on the method of antigen delivery, DCs stimulate immune responses or induce tolerance. As a consequence of the dual function of DCs, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. In vaccine development, a major aim is to induce strong, specific T-cell responses. This is achieved by targeting antigen to cell surface molecules on DCs that efficiently channel the antigen into endocytic compartments for loading onto MHC molecules and stimulation of T-cell responses. The most attractive cell surface receptors, expressed on DCs used as targets for antigen delivery for cancer and other diseases, are discussed. Vasso Apostolopoulos, Theresia Thalhammer, Andreas G. Tzakos, and Lily Stojanovska Copyright © 2013 Vasso Apostolopoulos et al. All rights reserved. Targeted Antiepidermal Growth Factor Receptor (Cetuximab) Immunoliposomes Enhance Cellular Uptake In Vitro and Exhibit Increased Accumulation in an Intracranial Model of Glioblastoma Multiforme Mon, 23 Sep 2013 13:49:12 +0000 Therapeutic advances do not circumvent the devastating fact that the survival rate in glioblastoma multiforme (GBM) is less than 5%. Nanoparticles consisting of liposome-based therapeutics are provided against a variety of cancer types including GBM, but available liposomal formulations are provided without targeting moieties, which increases the dosing demands to reach therapeutic concentrations with risks of side effects. We prepared PEGylated immunoliposomes (ILs) conjugated with anti-human epidermal growth factor receptor (EGFR) antibodies Cetuximab (α-hEGFR-ILs). The affinity of the α-hEGFR-ILs for the EGF receptor was evaluated in vitro using U87 mg and U251 mg cells and in vivo using an intracranial U87 mg xenograft model. The xenograft model was additionally analyzed with respect to permeability to endogenous albumin, tumor size, and vascularization. The in vitro studies revealed significantly higher binding of α-hEGFR-ILs when compared with liposomes conjugated with isotypic nonimmune immunoglobulin. The uptake and internalization of the α-hEGFR-ILs by U87 mg cells were further confirmed by 3D deconvolution analyses. In vivo, the α-hEGFR-ILs accumulated to a higher extent inside the tumor when compared to nonimmune liposomes. The data show that α-hEGFR-ILs significantly enhance the uptake and accumulation of liposomes in this experimental model of GBM suggestive of improved specific nanoparticle-based delivery. Joachim Høg Mortensen, Maria Jeppesen, Linda Pilgaard, Ralf Agger, Meg Duroux, Vladimir Zachar, and Torben Moos Copyright © 2013 Joachim Høg Mortensen et al. All rights reserved. The Effect of Polymer Content on the Non-Newtonian Behavior of Acetaminophen Suspension Tue, 10 Sep 2013 08:29:17 +0000 Acetaminophen is used as an analgesic and antipyretic agent. The aim of the study was evaluation of the effect of different polymers on rheological behavior of acetaminophen suspension. In order to achieve controlled flocculation, sodium chloride was added. Then structural vehicles such as carboxymethyl cellulose (CMC), polyvinyl pyrrolidone (PVP), tragacanth, and magnesium aluminum silicate (Veegum) were evaluated individually and in combination. Physical stability parameters such as sedimentation volume (), redispersibility (), and growth of crystals of the suspensions were determined. Also, the rheological properties of formulations were studied. The results of this study showed that the combination of suspending agents had the most physical stability and pseudoplastic behavior with some degree of thixotropy. Viscosity of suspensions was increased by adding NaCl 0.02%. Presence of PVP is necessary for improving rheological behavior of suspensions by NaCl. This may be related to the cross-linking between the carbonyl group in the PVP segment and Na+ ions. Eskandar Moghimipour, Maryam Kouchak, Anayatollah Salimi, Saeed Bahrampour, and Somayeh Handali Copyright © 2013 Eskandar Moghimipour et al. All rights reserved. Critical Assessment of Implantable Drug Delivery Devices in Glaucoma Management Mon, 26 Aug 2013 15:35:30 +0000 Glaucoma is a group of heterogeneous disorders involving progressive optic neuropathy that can culminate into visual impairment and irreversible blindness. Effective therapeutic interventions must address underlying vulnerability of retinal ganglion cells (RGCs) to degeneration in conjunction with correcting other associated risk factors (such as elevated intraocular pressure). However, realization of therapeutic outcomes is heavily dependent on suitable delivery system that can overcome myriads of anatomical and physiological barriers to intraocular drug delivery. Development of clinically viable sustained release systems in glaucoma is a widely recognized unmet need. In this regard, implantable delivery systems may relieve the burden of chronic drug administration while potentially ensuring high intraocular drug bioavailability. Presently there are no FDA-approved implantable drug delivery devices for glaucoma even though there are several ongoing clinical studies. The paper critically assessed the prospects of polymeric implantable delivery systems in glaucoma while identifying factors that can dictate (a) patient tolerability and acceptance, (b) drug stability and drug release profiles, (c) therapeutic efficacy, and (d) toxicity and biocompatibility. The information gathered could be useful in future research and development efforts on implantable delivery systems in glaucoma. Dharani Manickavasagam and Moses O. Oyewumi Copyright © 2013 Dharani Manickavasagam and Moses O. Oyewumi. All rights reserved. Development of Oral Sustained Release Rifampicin Loaded Chitosan Nanoparticles by Design of Experiment Sun, 18 Aug 2013 11:25:42 +0000 Objective. The main objective of the present investigation was to develop and optimize oral sustained release Chitosan nanoparticles (CNs) of rifampicin by design of experiment (DOE). Methodology. CNs were prepared by modified emulsion ionic gelation technique. Here, inclusion of hydrophobic drug moiety in the hydrophilic matrix of polymer is applied for rifampicin delivery using CN. The 23 full-factorial design was employed by selecting the independent variables such as Chitosan concentration (), concentration of tripolyphosphate (), and homogenization speed () in order to achieve desired particle size with maximum percent entrapment efficiency and drug loading. The design was validated by checkpoint analysis, and formulation was optimized using the desirability function. Results. Particle size, drug entrapment efficiency, and drug loading for the optimized batch were found to be 221.9 nm, 44.17 ± 1.98% W/W, and 42.96 ± 2.91% W/W, respectively. In vitro release data of optimized formulation showed an initial burst followed by slow sustained drug release. Kinetic drug release from CNs was best fitted to Higuchi model. Conclusion. Design of Experiment is an important tool for obtaining desired characteristics of rifampicin loaded CNs. In vitro study suggests that oral sustained release CNs might be an effective drug delivery system for tuberculosis. Bhavin K. Patel, Rajesh H. Parikh, and Pooja S. Aboti Copyright © 2013 Bhavin K. Patel et al. All rights reserved. Infuence of Microstructure in Drug Release Behavior of Silica Nanocapsules Tue, 06 Aug 2013 10:40:56 +0000 Meso- and nanoporous structures are adequate matrices for controlled drug delivery systems, due to their large surface areas and to their bioactive and biocompatibility properties. Mesoporous materials of type SBA-15, synthesized under different pH conditions, and zeolite beta were studied in order to compare the different intrinsic morphological characteristics as pore size, pore connectivity, and pore geometry on the drug loading and release process. These materials were characterized by X-ray diffraction, nitrogen adsorption, scanning and transmission electron microscopy, and calorimetric measurements. Ibuprofen (IBU) was chosen as a model drug for the formulation of controlled-release dosage forms; it was impregnated into these two types of materials by a soaking procedure during different periods. Drug loading and release studies were followed by UV-Vis spectrophotometry. All nano- and mesostructured materials showed a similar loading behavior. It was found that the pore size and Al content strongly influenced the release process. These results suggest that the framework structure and architecture affect the drug adsorption and release properties of these materials. Both materials offer a good potential for a controlled delivery system of ibuprofen. Gema Gonzalez, Amaya Sagarzazu, and Tamara Zoltan Copyright © 2013 Gema Gonzalez et al. All rights reserved. Lipid-Based Nanoparticles in Cancer Diagnosis and Therapy Tue, 09 Jul 2013 10:57:37 +0000 Today, researchers are constantly developing new nanomaterials, nanodevices, and nanoparticles to meet unmet needs in the delivery of therapeutic agents and imaging agents for cancer therapy and diagnosis, respectively. Of particular interest here are lipid-based nanoparticles (LNPs) that are genuine particles (approximately 100 nm in dimension) assembled from varieties of lipid and other chemical components that act collectively to overcome biological barriers (biobarriers), in order for LNPs to preferentially accumulate in or around disease-target cells for the functional delivery of therapeutic agents for treatment or of imaging agents for diagnosis. The capabilities of these LNPs will clearly vary depending on functional requirements, but the nanoscale allows for an impressive level of diversity in capabilities to enable corresponding LNPs to address an equally diverse range of functional requirements. Accordingly, LNPs should be considered appropriate vehicles to provide an integrated, personalized approach to cancer diagnosis and therapy in future cancer disease management. Andrew D. Miller Copyright © 2013 Andrew D. Miller. All rights reserved. Polymeric Micelles, a Promising Drug Delivery System to Enhance Bioavailability of Poorly Water-Soluble Drugs Thu, 27 Jun 2013 08:24:08 +0000 Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained. Wei Xu, Peixue Ling, and Tianmin Zhang Copyright © 2013 Wei Xu et al. All rights reserved. Enhanced Dendritic Cell-Mediated Antigen-Specific CD4+ T Cell Responses: IFN-Gamma Aids TLR Stimulation Tue, 28 May 2013 10:31:45 +0000 Phenotypic maturation and T cell stimulation are two functional attributes of DCs critical for immune induction. The combination of antigens, including those from cancer, with Toll-like receptor (TLR) ligands induces far superior cellular immune responses compared to antigen alone. In this study, IFN-gamma treatment of bone marrow-derived DC, followed by incubation with the TLR2, TLR4, or TLR9 agonists, enhanced DC activation compared to TLR ligation alone. Most notably, the upregulation of CD40 with LPS stimulation and CD86 with CpG stimulation was observed in in vitro cultures. Similarly, IFN-gamma coinjected with TLR ligands was able to promote DC activation in vivo, with DCs migrating from the site of immunization to the popliteal lymph nodes demonstrating increased expression of CD80 and CD86. The heightened DC activation translated to a drastic increase in T cell stimulatory capacity in both antigen independent and antigen dependent fashions. This is the first time that IFN-gamma has been shown to have a combined effect with TLR ligation to enhance DC activation and function. The results demonstrate the novel use of IFN-gamma together with TLR agonists to enhance antigen-specific T cell responses, for applications in the development of enhanced vaccines and drug targets against diseases including cancer. Kuo-Ching Sheng, Stephanie Day, Mark D. Wright, Lily Stojanovska, and Vasso Apostolopoulos Copyright © 2013 Kuo-Ching Sheng et al. All rights reserved.