pH responsive cylindrical MSN for oral delivery of insulin-design, fabrication and evaluation

Objective: The objective of the present study was to develop novel PMV [poly (methacrylic acid-co-vinyl triethoxylsilane)]-coated mesoporous silica nanoparticles (MSN) with improved hypoglycemic effect for oral insulin (INS) delivery. Methods: MSN was synthesized under acidic condition using Pluronic (R) P 123 and Tetra ethoxy orthosilane. Surfactant was removed by calcination. Calcined MSN was coated with pH sensitive polymer PMV. Cytotoxicity of this coated MSN was evaluated by MTT assay using CHO-K1 cell line. Different MSN samples were characterized with BET surface area analyzer, FESEM, TEM, FT-IR, XRD, TG-DTA. In vivo study was performed using male rats. Pharmacokinetic study was conducted using HPLC. Results and discussion: Highest surface area (304.3921 m(2)/g) was observed in case of calcined sample. Adsorption pore width of final coated sample was highest (64.7844nm) compared with others. No noticeable cytotoxicity was observed for this coated support. The entrapment efficiency of insulin was found to be 39.39%. In vitro studies were done at different pH using Franz-diffusion cell. Results showed significant release at pH 7.4. Cumulative drug release over a period of 6h was more than 48% at this systemic pH. Effect of this MSN-PMV-INS on blood glucose level was retained for 16h. This novel formulation has shown 73.10% relative bioavailability of insulin. Conclusion: A novel-coated mesoporous silica support was successfully developed for delivery of insulin through oral route.