Behzad Jafari1, Farzaneh Rafie, Soodabeh Davaran. 1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ; Faculty of Pharmacy, 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.
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.
Entities:
Keywords:
Hydrogel; Insulin; NIPAAm; Oral Drug Delivery
Authors: Mariko Morishita; Takahiro Goto; Koji Nakamura; Anthony M Lowman; Kozo Takayama; Nicholas A Peppas Journal: J Control Release Date: 2005-12-02 Impact factor: 9.776