Aim: Although the oral route for insulin delivery is the most convenient, directly administered oral insulin is degraded by proteolytic enzymes in the gastrointestinal (GI) tract. Polylactide was prepared in order to microcapsulate the insulin to avoid the enzymes in the GI. The physical characteristics 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 solvent extraction. Its morphologic character was observed by scanning electron microscopy (SEM). The insulin release profile was determined in vitro by insulin measurement and in vivo by blood glucose measurement after the force-feeding of 66 diabetic rats.
Results: When the microcapsule was spherical in shape (diameter 1.5-2.0 microm) 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 peak release rates of 65-74% over 6-8 h in phosphate buffer. The same dose of PLA-MCI (insulin 2.5 mg) led to decreased responses (from 28% to 68% of control 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 mg 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 degradation by the proteolytic enzymes in the GI and of alleviating hyperglycaemia for a prolonged period of time in diabetic rats. It may therefore be considered as a new carrier for oral insulin.