Dextran-b-poly(lactide-co-glycolide) polymersome for oral delivery of insulin: In vitro and in vivo evaluation

Insulin is the first line therapy in type 1 diabetes and usually patients suffer from three or more daily insulin injections. It is obvious that patient compliance can be improved greatly if insulin could be formulated in an oral dosage form. In the current study, polymersomes based on amphiphilic copolymers of dextran (DEX)5000–poly(lactic-co-glycolic acid) (PLGA)13,000 and DEX25000–PLGA48000 were synthesized and used for the encapsulation of insulin. The polymersomes were prepared using a modified direct hydration method by blending an aqueous solution of insulin with DEX–PLGA copolymers at room temperature. The in vitro insulin release through the nanopolymersomal system was studied in HCl 0.1N (pH1.2) and phosphate buffered saline (pH7.4). The results demonstrated that the average insulin encapsulation efficiency was >90%. The in vitro release experiment demonstrated that while insulin release in the simulated gastric condition was negligible, a significant amount of insulin was released in the simulated intestinal condition. According to the results of a circular dichroism test, secondary and tertiary structures of the released insulin were identical to that of standard insulin. Permeability studies across MDCK cells showed that permeability levels after 240min were 16.89±0.39% with DEX5000–PLGA13000 and 9.34±0.79% with DEX25000–PLGA48000, indicating a noticeable increase compared with free insulin. Significant hypoglycemic effects in the in vivo diabetic rat model revealed the efficacy of the DEX–PLGA-based polymersomes as oral insulin carriers. Thus, insulin-loaded, self-assembled DEX–PLGA polymersomes showed promising in vitro and in vivo efficiency and can be considered as a potential oral insulin carrier system. [Display omitted]