胰岛素柔性纳米脂质体的口腔给药研究

目的探讨柔性纳米脂质体经口腔粘膜转运蛋白多肽类药物的可能性。方法用反相蒸发法制备胰岛素柔性纳米脂质体和普通脂质体,对其包封率、形态和粒径大小进行测定。以家兔为动物模型,口腔给药(bu)后,进行体内降糖实验,同时测定胰岛素水平变化。结果胰岛素柔性纳米脂质体与普通脂质体的包封率分别为(18.9±1.8)%和(22.1±2.2)%;粒径分别为(42±20) nm和(60±34) nm。透射电镜下,胰岛素柔性纳米脂质体的指纹状结构比普通脂质体更多,其他无明显区别。以sc胰岛素溶液(1 U·kg^-1)为对照,bu胰岛素柔性纳米脂质体组(10 U·kg^-1)的药理相对生物利用度为15.59%,相对生物利用度为19.78%,高于bu胰岛素溶液对照组(P<0.05)、胰岛素普通脂质体组(P<0.05)及空白柔性纳米脂质体与胰岛素混合物组(P<0.05)。结论胰岛素柔性纳米脂质体可能成为经口腔粘膜转运蛋白多肽类药物的有效载体。

STUDIES ON BUCCAL DELIVERY OF INSULIN FLEXIBLE NANOLIPOSOMES

AIMTo investigate the possibility of the enhancing effect of flexible nanoliposomes on buccal delivery of insulin. METHODSTwo kinds of liposomes (flexible nanoliposomes and conventional liposomes) were prepared by reverse-phase evaporation methods. The liposomal entrapment efficiency was determined by column chromatography. The particle sizes and the morphology of the liposomes were also evaluated. The hypoglycemic effect and the changes of insulin concentration in vivo of insulin liposomes on rabbits were investigated. RESULTSThe entrapment efficiencies of the flexible and conventional liposomes were (18.9±1.8)% (N=3) and (22.1±2.2)% (N=3), respectively. The particle sizes of the flexible and conventional liposomes were (42±20) nm and (60±34) nm, respectively. There were no significant differences of appearance between two liposomes. Compared to subcutaneous administration of insulin solution, the relative pharmacological bioavailability and the relative bioavailability of insulin-flexible nanoliposomes group were 15.59% and 19.78%, respectively. The insulin-flexible nanoliposomes group was higher than both insulin conventional liposomes group (P<0.05) and blank flexible nanoliposomes and insulin mixture group (P<0.05).CONCLUSIONThe flexible nanoliposome may be a better carrier for buccal delivery of protein drugs than the conventional liposome.