Journal of Drug Delivery The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . 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. Nanotechnologies in Cancer Mon, 13 May 2013 10:57:27 +0000 Giuseppe De Rosa, Michele Caraglia, Stefano Salmaso, and Tamer Elbayoumi Copyright © 2013 Giuseppe De Rosa et al. All rights reserved. MRI-Guided Focused Ultrasound as a New Method of Drug Delivery Sun, 12 May 2013 10:21:06 +0000 Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery. M. Thanou and W. Gedroyc Copyright © 2013 M. Thanou and W. Gedroyc. All rights reserved. Nanoparticle Albumin Bound Paclitaxel in the Treatment of Human Cancer: Nanodelivery Reaches Prime-Time? Thu, 02 May 2013 15:30:37 +0000 Nanoparticle albumin bound paclitaxel (nab-paclitaxel) represents the first nanotechnology-based drug in cancer treatment. We discuss the development of this innovative compound and report the recent changing-practice results in breast and pancreatic cancer. A ground-breaking finding is the demonstration that nab-paclitaxel can not only enhance the activity and reduce the toxicity of chromophore-diluted compound, but also exert activity in diseases considered refractory to taxane-based treatment. This is the first clinical demonstration of major activity of nanotechnologically modified drugs in the treatment of human neoplasms. Iole Cucinotto, Lucia Fiorillo, Simona Gualtieri, Mariamena Arbitrio, Domenico Ciliberto, Nicoletta Staropoli, Anna Grimaldi, Amalia Luce, Pierfrancesco Tassone, Michele Caraglia, and Pierosandro Tagliaferri Copyright © 2013 Iole Cucinotto et al. All rights reserved. Cosmetotextiles with Gallic Acid: Skin Reservoir Effect Thu, 11 Apr 2013 16:07:26 +0000 The antioxidant gallic acid (GA) has been incorporated into cotton (CO) and polyamide (PA) through two different vehicles, that is, liposomes and mixed micelles, and their respective absorption/desorption processes have been studied. Moreover, in vitro percutaneous absorption tests of different cosmetotextiles have been performed to demonstrate antioxidant penetration within the layers of the skin. When GA was embedded into the cosmetotextiles, it always promoted a reservoir effect that was much more marked than that observed for polyamide. Similar penetration was observed in the textiles treated with GA in mixed micelles or liposomes in such compartments of the skin as the stratum corneum, epidermis, and even the dermis. GA was detected in receptor fluid only when CO was treated with MM. This methodology may be useful in verifying how encapsulated substances incorporated into textile materials penetrate human skin. Indeed, such materials can be considered strategic delivery systems that release a given active compound into the skin at specific doses. Meritxell Martí, Cristina Alonso, Vanessa Martínez, Manel Lis, Alfons de la Maza, José L. Parra, and Luisa Coderch Copyright © 2013 Meritxell Martí et al. All rights reserved. Liposomal Doxorubicin in the Treatment of Breast Cancer Patients: A Review Mon, 25 Mar 2013 08:47:59 +0000 Drug delivery systems can provide enhanced efficacy and/or reduced toxicity for anticancer agents. Liposome drug delivery systems are able to modify the pharmacokinetics and biodistribution of cytostatic agents, increasing the concentration of the drug released to neoplastic tissue and reducing the exposure of normal tissue. Anthracyclines are a key drug in the treatment of both metastatic and early breast cancer, but one of their major limitations is cardiotoxicity. One of the strategies designed to minimize this side effect is liposome encapsulation. Liposomal anthracyclines have achieved highly efficient drug encapsulation and they have proven to be effective and with reduced cardiotoxicity, as a single agent or in combination with other drugs for the treatment of either anthracyclines-treated or naïve metastatic breast cancer patients. Of particular interest is the use of the combination of liposomal anthracyclines and trastuzumab in patients with HER2-overexpressing breast cancer. In this paper, we discuss the different studies on liposomal doxorubicin in metastatic and early breast cancer therapy. Juan Lao, Julia Madani, Teresa Puértolas, María Álvarez, Alba Hernández, Roberto Pazo-Cid, Ángel Artal, and Antonio Antón Torres Copyright © 2013 Juan Lao et al. All rights reserved. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids Mon, 25 Mar 2013 08:21:31 +0000 Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed. Joana R. Viola, Diana F. Rafael, Ernst Wagner, Robert Besch, and Manfred Ogris Copyright © 2013 Joana R. Viola et al. All rights reserved. Clinical Trials with Pegylated Liposomal Doxorubicin in the Treatment of Ovarian Cancer Thu, 14 Mar 2013 09:22:52 +0000 Among the pharmaceutical options available for treatment of ovarian cancer, increasing attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation prolongs the persistence of the drug in the circulation and potentiates intratumor accumulation. Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. In 1999 it was first approved for platinum-refractory ovarian cancer and then received full approval for platinum-sensitive recurrent disease in 2005. PLD remains an important therapeutic tool in the management of recurrent ovarian cancer in 2012. Recent interest in PLD/carboplatin combination therapy has been the object of phase III trials in platinum-sensitive and chemonaïve ovarian cancer patients reporting response rates, progressive-free survival, and overall survival similar to other platinum-based combinations, but with a more favorable toxicity profile and convenient dosing schedule. This paper summarizes data clarifying the role of pegylated liposomal doxorubicin (PLD) in ovarian cancer, as well as researches focusing on adding novel targeted drugs to this cytotoxic agent. Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Carla Cavaliere, Rosa Tambaro, Gaetano Facchini, Cono Scaffa, Simona Losito, Antonio Pizzolorusso, and Sandro Pignata Copyright © 2013 Carmela Pisano et al. All rights reserved. Lipid-Based Nanovectors for Targeting of CD44-Overexpressing Tumor Cells Thu, 07 Mar 2013 14:45:20 +0000 Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that exists in living systems, and it is a major component of the extracellular matrix. The hyaluronic acid receptor CD44 is found at low levels on the surface of epithelial, haematopoietic, and neuronal cells and is overexpressed in many cancer cells particularly in tumour initiating cells. HA has been therefore used as ligand attached to HA-lipid-based nanovectors for the active targeting of small or large active molecules for the treatment of cancer. This paper describes the different approaches employed for the preparation, characterization, and evaluation of these potent delivery systems. Silvia Arpicco, Giuseppe De Rosa, and Elias Fattal Copyright © 2013 Silvia Arpicco et al. All rights reserved. Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting Thu, 07 Mar 2013 11:11:32 +0000 Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor’s vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies. Federico Perche and Vladimir P. Torchilin Copyright © 2013 Federico Perche and Vladimir P. Torchilin. All rights reserved. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers Thu, 07 Mar 2013 08:42:09 +0000 Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed. Stefano Salmaso and Paolo Caliceti Copyright © 2013 Stefano Salmaso and Paolo Caliceti. All rights reserved. Bisphosphonates and Cancer: What Opportunities from Nanotechnology? Mon, 04 Mar 2013 13:58:15 +0000 Bisphosphonates (BPs) are synthetic analogues of naturally occurring pyrophosphate compounds. They are used in clinical practice to inhibit bone resorption in bone metastases, osteoporosis, and Paget's disease. BPs induce apoptosis because they can be metabolically incorporated into nonhydrolyzable analogues of adenosine triphosphate. In addition, the nitrogen-containing BPs (N-BPs), second-generation BPs, act by inhibiting farnesyl diphosphate (FPP) synthase, a key enzyme of the mevalonate pathway. These molecules are able to induce apoptosis of a number of cancer cells in vitro. Moreover, antiangiogenic effect of BPs has also been reported. However, despite these promising properties, BPs rapidly accumulate into the bone, thus hampering their use to treat extraskeletal tumors. Nanotechnologies can represent an opportunity to limit BP accumulation into the bone, thus increasing drug level in extraskeletal sites of the body. Thus, nanocarriers encapsulating BPs can be used to target macrophages, to reduce angiogenesis, and to directly kill cancer cell. Moreover, nanocarriers can be conjugated with BPs to specifically deliver anticancer agent to bone tumors. This paper describes, in the first part, the state-of-art on the BPs, and, in the following part, the main studies in which nanotechnologies have been proposed to investigate new indications for BPs in cancer therapy. Giuseppe De Rosa, Gabriella Misso, Giuseppina Salzano, and Michele Caraglia Copyright © 2013 Giuseppe De Rosa et al. All rights reserved. Cancer Epigenetics: New Therapies and New Challenges Tue, 26 Feb 2013 16:03:58 +0000 Cancer is nowadays considered to be both a genetic and an epigenetic disease. The most well studied epigenetic modification in humans is DNA methylation; however it becomes increasingly acknowledged that DNA methylation does not work alone, but rather is linked to other modifications, such as histone modifications. Epigenetic abnormalities are reversible and as a result novel therapies that work by reversing epigenetic effects are being increasingly explored. The biggest clinical impact of epigenetic modifying agents in neoplastic disorders thus far has been in haematological malignancies, and the efficacy of DNMT inhibitors and HDAC inhibitors in blood cancers clearly attests to the principle that therapeutic modification of the cancer cell epigenome can produce clinical benefit. This paper will discuss the most well studied epigenetic modifications and how these are linked to cancer, will give a brief overview of the clinical use of epigenetics as biomarkers, and will focus in more detail on epigenetic drugs and their use in solid and blood cancers. Eleftheria Hatzimichael and Tim Crook Copyright © 2013 Eleftheria Hatzimichael and Tim Crook. All rights reserved.