Preliminary study of oral polylactide microcapsulated insulin in vitro andin vivo

Aim: Although the oral route for insulin delivery is the most convenient, d irectly administered oral insulin is degraded by proteolytic enzymes in the gastrointestinal (GI) tract. Polylactide was prepared in order to microcap sulate the insulin to avoid the enzymes in the GI. The physical characteris tics and therapeutic possibilities of polylactide microcapsulated insulin ( PLA-MCI) were studied in vivo and in vitro. Methods: PLA-MCI was prepared by the two-step method of emulsion and solven t extraction. Its morphologic character was observed by scanning electron m icroscopy (SEM). The insulin release profile was determined in vitro by ins ulin measurement and in vivo by blood glucose measurement after the force-f eeding of 66 diabetic rats. Results: When the microcapsule was spherical in shape (diameter 1.5-2.0 mu m) the entrapment efficiency of insulin was 90% and the loading rate was 10 % (W/W). The PLA-MCI (which contained 3.0 units of insulin/mg of PLA) had p eak release rates of 65-74% over 6-8 h in phosphate buffer. The same dose o f PLA-MCI (insulin 2.5 mg) led to decreased responses (from 28% to 68% of c ontrol blood glucose levels) in the level of blood glucose in 32 rats which had not fasted after they had been force-fed. When 1.2, 1.8, 2.2 and 3.0 m g of insulin + PLA-MCI was administered to eight diabetic rats, their blood glucose levels decreased by 28%, 36%, 54% and 78%, respectively. Conclusions: PLA microcapsules are capable of protecting insulin from degra dation by the proteolytic enzymes in the GI and of alleviating hyperglycaem ia for a prolonged period of time in diabetic rats. It may therefore be con sidered as a new carrier for oral insulin.