Behzad Jafari
1,2, Farzaneh Rafie
1,2, Soodabeh Davaran
2,3*1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3 Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Introduction: Over the past years, temperature and pH-sensitive hydrogels was developed as suitable carriers for drug delivery. In this study temperature and pH-sensitive hydrogels was designed for an oral insulin delivery modeling. Methods: NIPAAm-MAA -HEM copolymers were synthesized by radical chain reaction with 86:4:10 (5% w/v) ratios respectively. Reaction was carried out in 1,4-Dioxane under Nitrogen gas-flow. The copolymers were characterized with FT-IR, 1H-NMR and DSC. Copolymers were loaded with regular insulin by modified double emulsion method with ratio of 1:10. Release study carried out in two different pH (pH=2 and 7.4 for stomach and intestine simulation respectively) at 37ºC. For each pH, a 5 mL suspension of the insulin containing hydrogel was taken in to a cellulose acetate dialysis membrane, and the dialysis membrane was allowed to float in a beaker containing 15 mL of buffer solution. The beakers were placed in a shaker incubator maintained at 37ºC. Phosphate buffer (0.1 M, pH 3)/ acetonitrile (60/40) was used as the mobile phase in HPLC assay. Results: Yield of reaction was 86% with an optimum Lower Critical Solution Temperature point (30ºC). In-vitro studies showed a control release behavior via pH changes which the amount of insulin releases was 80% and 20% at pH=2 and 7.4 respectively. Conclusion: Results showed that by optimizing polymerization and loading method we could achieve a suitable nano system for oral delivery of insulin.