胰岛素聚氰基丙烯酸正丁酯纳米粒在油介质中的稳定性及其对糖尿病大鼠的降血糖作用

目的通过对胰岛素聚氰基丙烯酸正丁酯纳米粒(IPN)在油介质(含有0.5%吐温-20和5%维生素E的豆油)中的稳定性及其口服后对链脲霉素引起的糖尿病大鼠降血糖作用的研究，希望得到一种稳定而有效的胰岛素纳米粒口服制剂。方法依据IPN中的胰岛素含量，IPN的平均粒径和粒子跨度，及其体外释药来评估其稳定性。将IPN分散在含有0.5% 吐温-20，pH 2.0的水溶液中作为对照。结果研究表明，不论样品是在(25±2) ℃条件下避光放置1年，还是在体外与3种消化道酶37 ℃酶解30 min，油介质中的IPN都比水介质中IPN稳定性好。依据单剂量po给药后，在0-144 h血糖降低的百分数与时间曲线上面积(AAC)可知，po IPN的油溶液(50 u·kg^-1)相对于sc胰岛素(2 u·kg^-1)的生物利用度为22.4%，明显高于po IPN水溶液的相对生物利用度(15.5%)。结论分散在油介质中的IPN具有较好的稳定性和相对较高的生物利用度，因此，含有0.5%吐温-20和5%维生素E的豆油有望成为口服胰岛素聚氰基丙烯酸正丁酯纳米粒的有效而稳定的分散介质。

The stability of insulin-loaded polybutylcyanoacrylate nanoparticles in an oily medium and the hypoglycemic effect in diabetic rats

AIM: To study the stability of insulin-loaded polybutylcyanoacrylate nanoparticles (IPN) in an oily medium (soybean oil containing 0.5% (v/v) Tween-20 and 5% (v/v) Vitamin E) along with the hypoglycemic effect following their oral administration to streptozotocin (STZ) induced diabetic rats. METHODS: The stability of IPN in the process was appraised by measurement of the amount of undegraded insulin associated to nanoparticles, the average size and the span of IPN, as well as the release of insulin from IPN. IPN in an aqueous medium (containing 0.5% (v/v) Tween-20) at pH 2.0 was also investigated as control. RESULTS: The study showed that IPN in the oily medium was more stable than that in the aqueous medium over one year of storage in the dark at (25 +/- 2) degrees C and the in vitro stability of IPN in the oily medium against degradation by proteolytic enzymes was much better than that in the aqueous medium. The apparent bioavailability of an oral administration of IPN (50 u x kg(-1)) in the oily medium versus an (sc) injection of insulin (2 u x kg(-1)) was 22.4%, much higher than that of IPN in the aqueous medium (15.5%), based on decreased areas above curve (AAC) determination for the blood glucose depression from time zero to 144 h of a single oral administration of IPN to STZ-diabetic rats. CONCLUSION: IPN in soybean oil containing Tween-20 (0.5% v/v) and Vitamin E (5% v/v) could be considered as an effective and stable delivery system for oral insulin.