Predictive modeling of insulin release profile from cross-linked chitosan microspheres.

Insulin-loaded microspheres composed of chitosan 3% (w/v), and loading 120 IU insulin were produced by emulsion cross-linking method. Cross-linking time was 5 h and glutaraldehyde 3.5% (v/v) was used as cross-linker. Swelling ratio studies were evaluated to predict release of insulin from chitosan microspheres. Bacitracin and sodium taurocholate were incorporated in the formulations as proteolytic enzyme inhibitor and absorption enhancer, respectively. In vitro insulin release studies were performed in phosphate buffer pH 7.4 and also in HCl pH 2 with and without trypsin. Activity of bacitracin was also evaluated. In vitro release showed a controlled profile up to 12 h and the formulation containing 0.15% (w/v) of bacitracin revealed a maximum biological activity of about 49.1 ± 4.1%. Mathematical modeling using Higuchi and Korsmeyer-Peppas suggested a non-Fickian diffusion as the mechanism of insulin release. Insulin-loaded chitosan microspheres for oral delivery showed to be an innovative and reliable delivery system to overcome conventional insulin therapy.

Cross-linked chitosan microspheres for oral delivery of insulin: Taguchi design and in vivo testing.

Insulin-loaded chitosan microspheres were engineered by emulsion cross-linking method using glutaraldehyde as cross-linker. Taguchi orthogonal method was applied to optimize the production time and reduce the number of experiments required to obtain an optimized formulation. Three variables were evaluated, i.e. chitosan and glutaraldehyde concentrations, and cross-linking time at three levels. The dependent variables were the mean particle size and the encapsulation efficiency. The optimal formulation was obtained with chitosan 3% (w/v), glutaraldehyde 3.5% (v/v), and cross-linking time of 5h, characterized by microspheres with a mean particle size of 29.5 µm, and insulin encapsulation efficiency of 71.6±1.3%. In vivo studies were carried out using male Wistar albino rats, revealing a significant reduction in blood glucose level after administration of the optimized formulation, in comparison to a subcutaneous insulin injection. Chitosan microspheres were superior in terms of sustaining protein release over conventional insulin therapy.

Formulation, characterization and optimization of hepatitis B surface antigen (HBsAg)-loaded chitosan microspheres for oral delivery.

CONTEXT: Approximately 400 million persons worldwide have chronic hepatitis B. This is due to problems associated with vaccine delivery, stability and cost. Hence the present challenge in vaccinology is to develop safer, cheaper and easy-to-deliver forms of vaccines. A novel needle-free oral vaccine will be an ideal tool to fight this silent killer disease. OBJECTIVE: The aim of this work was to prepare and evaluate chitosan-loaded HBsAg microspheres for oral delivery. MATERIALS AND METHODS: Chitosan microspheres were prepared by emulsion solvent evaporation technique. To overcome the enzymatic and permeation barrier, protease inhibitors and permeation enhancers were also added. Studies were conducted to find the effect of stabilizer concentration, stirring speed, cross-linking agent and polymer concentration on microsphere size and entrapment efficiency. Formulations were characterized for their particle size, entrapment efficiency. They were also evaluated for the in vitro drug release, in vivo performances and the effect of different storage conditions. RESULTS: HBsAg-loaded chitosan microspheres with bacitracin as protease inhibitor showed better protective levels of immunity after oral administration comparing with aprotinin as protease inhibitor. Stability at room temperature up to a period of four months reduces incomplete vaccine coverage and logistic requirements. CONCLUSION: The study signifies the potential of the formulated chitosan microspheres for effective oral administration of HBsAg.