Sanjay K. Jain

Design and development of solid lipid nanoparticles for topical delivery of an anti-fungal agent

Topical application of the drugs at the pathological sites offers potential advantages of delivering the drug directly to the site of action. The main aim of this work was to formulate and evaluate Miconazole nitrate (MN) loaded solid lipid nanoparticles (SLN) for topical application. MN-loaded SLN were prepared by modified solvent injection method and characterized for shape, surface morphology, particle size, and drug entrapment. These solid lipid nanoparticles were spherical in shape with smooth surface and possessed mean average size of 206.39 ± 9.37 nm. In vitro drug release of MN-loaded SLN-bearing hydrogel was compared with MN suspension and MN hydrogel; MN-loaded SLN-bearing hydrogel depicted a sustained drug release over a 24-h period. Tape stripping experiments demonstrated 10-fold greater retention with MN-loaded SLN-bearing hydrogel as compared to MN suspension and MN hydrogel. The in vivo studies were performed by infecting the rats with candida species. It was observed that MN-loaded SLN-bearing hydrogel was more efficient in the treatment of candidiasis. Results indicate that MN-loaded SLN-bearing hydrogel provides a sustaining MN topical effect as well as quicker relief from fungal infection.

Enhanced Transdermal Delivery of Acyclovir Sodium via Elastic Liposomes

The elastic liposomes bearing acyclovir sodium were prepared for its enhanced transdermal delivery by conventional rotary evaporation method and characterized for various parameters such as vesicle shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, polydispersity index, turbidity and in vitro release pattern. Permeability studies of acyclovir sodium incorporated in elastic liposomes were performed across artificial membranes and rat skin. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy, that revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 160 μm) following channel like pathways. Skin permeation profile of elastic liposomal formulation bearing acyclovir sodium was observed and the investigations revealed an enhanced transdermal flux (6.21 ± 1.8 μg/cm2/hr) and decreased lag time (0.6 hr) for acyclovir sodium. The obtained flux was nearly 2.0 and 6.3 times higher than conventional liposomal formulation bearing acyclovir sodium and plain drug solution, respectively (p < 0.01). The elastic liposomal formulation for transdermal delivery of acyclovir sodium provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared with conventional liposomes. In vivo studies showed that on transdermal application of elastic liposomes, the concentration of acyclovir sodium in plasma was found to be 105 ± 9.4 ng/ml after 24 hr which is about 4.2 times compared with conventional liposomes. Thus it is concluded that the elastic liposomes may be promising vehicles for the transdermal delivery of acyclovir sodium.

Colonic targeting of metronidazole using azo aromatic polymers: Development and characterization

A system for colonic targeting of metronidazole was developed by coating the drug-containing capsules with azoaromatic and pH-sensitive polymers that are prone to selective degradation in the colon environment. The azoaromatic polymers were synthesized by a bulk polymerization technique using different ratios of water-soluble and water-insoluble monomers. These polymers were characterized for physical attributes, namely film-forming properties, effect of colon bacterial flora, and pH. These polymers were then used to coat the delivery system bearing metronidazole. The systems were subjected to in vitro release and in vivo performance studies. The studies revealed that azoaromatic polymers are cleaved by the colonic microbiota and can be used successfully for colonic targeting of metronidazole.

Targeted delivery of 5-ASA to colon using chitosan hydrogel microspheres

The present study is aimed at developing hydrogel microspheres of chitosan grafted with vinyl polymers for the controlled release of 5-ASA to the colon in rodents. The graft copolymer of chitosan with acrylamide was synthesized and used to prepare microspheres by water-in-oil (w/o) emulsification method (CHI-g-AAm). The microspheres were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, dynamic swelling and in vitro drug release. The prepared microspheres were spherical with smooth surfaces. The in vitro 5-ASA release from chitosan hydrogel microspheres exhibited significantly higher drug release in simulated colonic fluid containing caecal and colonic content than that in the simulated stomach and small intestinal fluid. Drug release in simulated fluids such as simulated intestinal fluid (SIF-pH 7.0), was found to be 84.4 ± 1.8% and 91.1 ± 1.3% in the presence of 5 and 10% rat caecal content (RCC), respectively, at the end of 8 h. The drug loaded microspheres were also studied for the healing of 2,4,6-trinitrobenzene sulfonic acid sodium salt (TNBS)-induced colitis in rats. The colonic injury and inflammation were assessed by measuring the myeloperoxidase (MPO) activity, colon wet weight/body weight (C/B) ratio and the damage score, respectively. Grafted chitosan microspheres bearing 5-ASA exhibited better therapeutic effects as evaluated by the MPO activities, C/B ratio and the damage score in comparison to 5ASA plain drug solution in oral administration.

Insulin Delivery Through the Ocular Route

The effect of insulin solution on the reduction of blood glucose concentration was studied after the administration of insulin solution through various routes-subcutaneous (SV), intravenous (IV), and ocular. Ocular administration of free insulin (400 U/mL) to normal rabbits produced no change in blood glucose level unless permeation enhancer was included in the dosing solution. Various concentrations of insulin were studied for their effectiveness on ocular administration and 10 U/kg dose was found to be optimum for ocular instillation. Among various penetration enhancers, poIyoxyethylene-9-lauryl ether (POE) in 0.8% w/w concentration exhibited better ocular compatibility and penetration-enhancing effect. The effectiveness of liposomes in aiding ocular absorption of entrapped insulin was studied in normal rabbits. Administration of insulin entrapped in positively charged liposomes composed of egg phosphatidylcholine with cholesterol and stearylamine (10: 2:1, in weight ratio) to normal rabbits produced substantial reduction in blood glucose concentration 90-120 min after the instillation of the formulation. In conclusion, it seems that administration of insulin in liposomes not only promotes the ocular absorption, but also controls and prolongs the drug action.

Engineered human erythrocytes as carriers for ciprofloxacin

AbstractCiprofloxacin (CFX), a broad-spectrum antibacterial agent, was loaded into human erythrocytes by a method based on hypotonic preswelling, hemolysis, isotonic resealing, and reannealing. Various parameters such as volume of aqueous drug solution added, drug concentration, and temperature were optimized to obtain maximum loading of drug into erythrocytes. The loaded cells were characterized for drug content, hemoglobin content, percent cell recovery, morphology, osmotic fragility, turbulence shock, and in vitro drug as well as hemoglobin efflux. No appreciable detrimental effects on cell morphology, osmotic fragility, and turbulence shock in comparison with normal cells were noted. Osmotic fragility and turbulence shock studies indicated that the loaded erythrocytes are less resistant than the normal erythrocytes. Glutaraldehyde treatment stabilized both types of cells with respect to drug and hemoglobin release, osmotic fragility, and turbulence fragility. The studies suggest the potential of CFX-l...

Polymeric nanocomposite: Development, characterization, ex vivo and in vivo evaluation for ulcerative colitis

ABSTRACT Chitosan nanoparticles (CH-NPs) and chitosan-montmorillonite nanocomposites (CH-MMT-NCPs) were developed and characterized. The in vitro drug release data revealed that the CH-MMT-NCPs successfully retarded the drug release until it entered into the simulated colonic fluid. Experimental colitis was induced by trinitrobenzenesulfonic acid (TNBS) into albino rats and clinical activity score and histological evaluation revealed that the CH-MMT-NCPs markedly improved the healing efficacy as compare to CH-NPs and drug solution. The CH-MMT-NCPs showed remarkable reduction in the ulcer index (3.80 ± 0.54) as compared to the CH-NPs (7.03 ± 0.78) and the group received MSZ solution (9.85 ± 0.58), respectively. GRAPHICAL ABSTRACT