ABSTRACT
BACKGROUND: Protein drugs such as insulin are usually used in the form of injection due to its low oral administration bioavailability. For the purpose of higher bioavailability, the common method is to encapsulate the drug into algitnate/chitosan microspheres, which introduced polysaccharides to accelerate biological absorption or reduce demolition of protease. OBJECTIVE: To construct alginate/chitosan microspheres containing cationic?-cyclodextrin polymer (CP?CD) /insulin complex for insulin oral delivery system, in addition, to inspect the influence of the charge density of cationic ?-cyclodextrin polymers on insulin release performance in vitro. DESIGN, TIME AND SETTING: The contrast observation experiment was performed at the Laboratory of Department of Polymer Science and Engineering, Sichuan University from November 2006 to July 2008. MATERIALS: ?-cyclodextrin, epichlorohydrin was supplied by Tianjin Bodi Chemical Industry Co., Ltd. Choline chloride and alginate was provided by Kelong Reagent Company, chitosan was purchased from Golden-shell Biochemical Co., Ltd. And insulin was produced by Wanbang Biochemical Pharmaceutical Company. METHODS: Cationic ?-cyclodextrin polymer was synthesized through a one-step polymerization of ?-cyclodextrin, epichlorohydrin and choline chloride. It was combined with insulin and then encapsulated into alginate/chitosan microspheres. In vitro insulin release behavior of the microsphere was studied in simulative gastrointestinal fluid. MAIN OUTCOME MEASURES: The entrapment efficiency, as well as insulin release in simulative gastrointestinal fluid. RESULTS: The charge density of CP?CD had a great impact on the insulin association efficiency of microspheres. The maximum association efficiency could reach (76.3?1.5)%. It showed that cumulative insulin release of microspheres containing CP?CD was less than that of the control group in simulated gastric fluid. The insulin released was 5.8 IU in simulated intestinal fluid, which was higher than the control group. CONCLUSION: Alginate/chitosan microsphere containing CP?CD/insulin complex is a promising system for improving insulin oral delivery efficiency.