Journal of drug delivery最新文献

Background. Oxybenzone, a broad spectrum sunscreen agent widely used in the form of lotion and cream, has been reported to cause skin irritation, dermatitis, and systemic absorption. Aim. The objective of the present study was to formulate oxybenzone loaded microsponge gel for enhanced sun protection factor with reduced toxicity. Material and Method. Microsponge for topical delivery of oxybenzone was successfully prepared by quasiemulsion solvent diffusion method. The effects of ethyl cellulose and dichloromethane were optimized by the 3(2) factorial design. The optimized microsponges were dispersed into the hydrogel and further evaluated. Results. The microsponges were spherical with pore size in the range of 0.10-0.22 µm. The optimized formulation possesses the particle size and entrapment efficiency of 72 ± 0.77 µm and 96.9 ± 0.52%, respectively. The microsponge gel showed the controlled release and was nonirritant to the rat skin. In creep recovery test it had shown highest recovery indicating elasticity. The controlled release of oxybenzone from microsponge and barrier effect of gel result in prolonged retention of oxybenzone with reduced permeation activity. Conclusion. Evaluation study revealed remarkable and enhanced topical retention of oxybenzone for prolonged period of time. It also showed the enhanced sun protection factor compared to the marketed preparation with reduced irritation and toxicity.

Dendrimers have shown great promise as drug delivery vehicles in recent years because they can be synthesized with designed size and functionalities for optimal transportation, targeting, and biocompatibility. One of the most well-known termini used for biocompatibility is polyethylene glycol (PEG), whose performance is affected by its actual conformation. However, the conformation of individual PEG bound to soft materials such as dendrimers has not been directly observed. Using atomic force microscopy (AFM) and scanning tunneling microscopy (STM), this work characterizes the structure adopted by PEGylated dendrimers with the highest resolution reported to date. AFM imaging enables visualization of the individual dendrimers, as well as the differentiation and characterization of the dendrimer core and PEG shell. STM provides direct imaging of the PEG extensions with high-resolution. Collectively, this investigation provides important insight into the structure of coated dendrimers, which is crucial for the design and development of better drug delivery vehicles.

To investigate the time dependence of sodium nitroprusside- (NPS-) induced oxidative effects, the authors study the variation of the antioxidant enzyme CAT activity in various tissues after the administration of a single 2.5 mg/kg dose of SNP or sodium chloride (NaCl 0.9%). For each of the two dosing times (1 and 13 hours after light onset, HALO, which correspond to the beginning of diurnal rest span and of nocturnal activity span of mice, resp.), brain, kidney, and liver tissues were excised from animals at 0, 1, 3, 6, 9, 12, 24, and 36 h following the drug administration and CAT activity was assayed. The results suggest that SNP-induced stimulation of CAT activity is greater in all three tissues when the drug is administered at 1 HALO than at 13 HALO. Two-way ANOVA revealed that CAT activity significantly (P < 0.004) varied as a function of the sampling time but not of the treatment in all three tissues. Moreover, a statistically significant (P < 0.004) interaction between the organ sampling-time and the SNP treatment was revealed in kidney regardless of the dosing time, whereas a highly significant (P < 0.0002) interaction was validated in liver only in animals injected at 13 HALO.

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.

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 (P < 0.05). 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.

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.

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 4.586 ± 0.08 μg/mL/cm(2) as compared to the control flux of 0.868 ± 0.06 μg/mL/cm(2). 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.

Objective. Objective of the present work was to develop site-specific gastroretentive drug delivery of Troxipide using polymers Pluronic F127 and Polyox 205 WSR. Troxipide is a novel gastroprotective agent with antiulcer, anti-inflammatory, and mucus secreting properties with elimination half-life of 7.4 hrs. Troxipide inhibits H. pylori-derived urease. It is mainly absorbed from stomach. Methods. 3(2) factorial design was applied to study the effect of independent variable. Effects of concentration of polymer on dependant variables as swelling index, hardness, and % drug release were studied. Pluronic F127 and Polyox 205 WSR were used as rate controlled polymer. Sodium bicarbonate and citric acid were used as effervescent-generating agent. Results. From the factorial batches, it was observed that formulation F5 (19% Pluronic F127 and 80% Polyox 205 WSR) showed optimum controlled drug release (98.60% ± 1.82) for 10 hrs with ability to float >12 hrs. Optimized formulation characterized by FTIR and DSC studies confirmed no chemical interactions between drug and polymer. Gastroretention for 6 hrs for optimized formulations was confirmed by in vivo X-ray placebo study. Conclusion. Results demonstrated feasibility of Troxipide in the development of gastroretentive site-specific drug delivery.

Breast cancer aberrantly expresses tissue factor (TF) in cancer tissues and cancer vascular endothelial cells (VECs). TF plays a central role in cancer angiogenesis, growth, and metastasis and, as such, is a target for therapy and drug delivery. TF is the cognate receptor of factor VIIa (fVIIa). We have coupled PTX (paclitaxel, also named Taxol) with a tripeptide, phenylalanine-phenylalanine-arginine chloromethyl ketone (FFRck) and conjugated it with fVIIa. The key aim of the work is to evaluate the antiangiogenic effects of PTX-FFRck-fVIIa against a PTX-resistant breast cancer cell line. Matrigel mixed with VEGF and MDA-231 was injected subcutaneously into the flank of athymic nude mice. Animals were treated by tail vein injection of the PTX-FFRck-fVIIa conjugate, unconjugated PTX, or PBS. The PTX-FFRck-fVIIa conjugate significantly reduces microvessel density in matrigel (p < 0.01-0.05) compared to PBS and unconjugated PTX. The breast cancer lung metastasis model in athymic nude mice was developed by intravenous injection of MDA-231 cells expressing luciferase. Animals were similarly treated intravenously with the PTX-FFRck-fVIIa conjugate or PBS. The conjugate significantly inhibits lung metastasis as compared to the control, highlighting its potential to antagonize angiogenesis in metastatic carcinoma. In conclusion, PTX conjugated to fVIIa is a promising therapeutic approach for improving selective drug delivery and inhibiting angiogenesis.

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.