Insulin controlled-release microcapsules to prolong the hypoglycemic effect in diabetic rats.

A solvent evaporation process was employed for preparing insulin microcapsules by using biodegradable polymers [polylactic acid (PLA), HP-55] and non-biodegradable polymers [ethylcellulose (EC), ethylenevinyl acetate (EVA)]. The release behavior of insulin microcapsules in pH 7.4 phosphate buffer solution was undertaken by a continuous flow column method. Seven types of insulin microcapsules were respectively injected into the flanks of fasting-diabetic SD rats induced by streptozotocin. The glucose levels and insulin concentrations in the blood were periodically sampled from the tail and assayed by a glucose analyzer and RIA method. Body weights were measured twice per week. The release rate was controllably dependent on the polymer used. The PLA microcapsules could maintain normoglycemia only for five days, whereas the (PLA + 1%EVA) microcapsules exhibited two times the hypoglycemic effect of PLA microcapsules, but (PLA + 1%EVA) microcapsules treated with 4% wax extended the duration of hypoglycemic effects for two weeks. There was no significant effect for insulin-HP-55 microcapsules. The EC microcapsules prolonged the hypoglycemic effect for 15 days, however, the (EC + 1%EVA) microcapsules could maintain the same effect for up to three weeks. The slower the release rate of insulin microcapsules in vitro the longer the hypoglycemic effect of insulin microcapsules in vivo. A close relationship between in vitro release behavior and in vivo hypoglycemic efficacy of insulin microcapsules was obtained.