Controlled release and hypoglycemic effect of insulin microcapsules constructed by dextran sulphate and ferric ion

Background: It is feasible to prepare the microsphere delivery system of protein and polypeptide drugs including insulin, by various proteolytic enzymes. This system may overcome such disadvantages as poor stability, short half-life time and the inactivation resuled in hydrolysis. Objective: To construct an insulin controlled microcapsule, and to investigate its in vitro controlled release and in vivo hypoglycemic effect. Design, time and setting: A controlled observation experiment was performed in Nanomedicine and Biosensor Laboratory, Bio-X Center, Harbin Institute of Technology between May 2007 and January 2008. Materials: Male Wistar rats were used to establish diabetes mellitus models by the intraperitoneal injection of streptozotocin. An insulin controlled microcapsule was fabricated by layer-by-layer self-assembly of dextran sulphate and ferric ion via electrostatic inter-action. Methods: The release effect of insulin-loaded microcapsules was detected by in vitro test. Eighteen diabetes mellitus models were divided into three groups randomly, and received subcutaneous injections of insulin 5 U/kg, subcutaneous injections of insulin 100 U/kg, and intragastric administration of insulin-loaded microcapsules 100 U/kg, respectively. Main outcome measures: The encapsulation efficiency, drug loading content, in vitro release behavior and in vivo hypoglycemic effect of the insulin-loaded microcapsules were all assessed. Results: The encapsulation efficiency and drug loading content of the insulin-loaded microcapsules were higher than 60% and 40%, respectively. The results of in vitro insulin releasing test displayed good release behavior, and drug release speed stepped down with the increase of encapsulation layers. The in vivo hypoglycemic effect study showed the insulin-loaded microcapsules significantly improved glucose tolerance to 6-10 hours by subcutaneous injection, while no effect was found after intragastric administration. Conclusion: Fabricated by layer-by-layer self-assembly of dextran sulphate and ferric ion via electrostatic interaction, the insulin-loaded microcapsules have a better stability, and could maintain the hypoglycemic effect for a long time.