口服胰岛素纳米脂质体的制备及其降血糖作用

目的改进胰岛素纳米脂质体的制备方法，考察脂质体经正常大鼠小肠给药和灌胃给药的降血糖效果。方法通过改变油相容积及油/水相比例，采用逆相蒸发-超声法制备了胰岛素纳米脂质体；测定了纳米脂质体的包封率；通过灌胃和小肠途径，给正常大鼠以350IU/kg的剂量，用酶-苯酚法测定大鼠血糖，并与空白纳米脂质体、胰岛素溶液及生理盐水相比较。结果胰岛素纳米脂质体的平均粒径为83.3nm，多分散系数为0.445，包封率为78.5%；大鼠灌胃给药后未能显示降血糖作用，但小肠给药后0.25h血糖下降37.6%±13.9%，0.5h血糖下降了89.3%±9.5%，维持50%左右降血糖水平2h，而同法给予的胰岛素溶液、生理盐水和空白纳米脂质体组均无降血糖作用。结论实验初步证实制备的纳米脂质体可以保护胰岛素在小肠中的活性并促进胰岛素吸收。

Preparation of Oral Insulin Nano-liposomes and Its Hypogly-cemic Effect

AIM: The present reseach was developed to prepare lecithinnano-liposomes encapsulating insulin and evaluate the enhancing effect of these vesicles on the absorption of hydrophilic proteins in the intestine. METHODS: Insulin nano-liposomes were prepared by reverse-phase evaporation and treated further by sonication. The content and entrapment efficiency of nano-liposomes were analyzed by HPLC. When liposomes were applied to the rats at a dose of 350IU/kg through both directly into the intestine and i.g. in vivo, the hypoglycemic effect was investigated. RESULTS: The particle size of nano-liposomes was 83.3nm with polydispersity index of 0.445. The entrapment efficiencies of nano-liposomes were 78.5%. In vivo hypoglycemic study showed the level of blood glucose reduced by nano-liposomes was 37.6%±13.9% at 0.25 h, reached 89.3%±9.5% at 0.5 h and remained less than 50% within 2 h. Blank nano-liposomes, insulin solution and saline had no hypoglycemic effect. CONCLUSION: Nano-liposomes may become a promising carrier for enhancing absorption of hydrophilic proteins in intestine.