生物素化脂质体作为潜在的胰岛素口服载体研究.pdfVIP

生物素化脂质体作为潜在的胰岛素口服载体的研究 张兴旺, 戚建平, 卢懿, 李晓阳, 何伟, 吴伟* 复旦大学药学院，教育部和全军智能化递药系统重点实验室，上海 201200 摘要：目的制备生物素修饰的胰岛素脂质体，考察其体外理化性质，体内降血糖效应和 生物利用度，研究其促进胰岛素吸收的机制。方法合成生物素— 硬脂酰磷脂酰乙醇胺 （biotin-DSPE ），制备含biotin-DSPE 的胰岛素脂质体，以粒径和包封率为指标确定最佳 处方，以 Caco-2 细胞模型考察其跨膜转运和细胞摄取性质，以糖尿病大鼠为模型考察脂 质体的体内降血糖效应和生物利用度。结果优化的胰岛素免疫脂质体提高了胰岛素的的 跨膜转运能力和增加量细胞摄取量，其体内相对药理生物利用度为 12.09%，生物利用度 达到 8.23%。结论生物素修饰的胰岛素脂质体能够通过受体介导的内吞机制促进胰岛素的 口服吸收，其作为生物大分子的口服传递载体具有潜在的应用前景。 关键词：胰岛素；脂质体；生物素；DSPE ；低血糖效应；生物利用度；糖尿病；受体介 导内吞 Biotinylated liposomes as potential carriers for oral delivery of insulin Xingwang Zhang, Jianping Qi, Yi Lu, Xiaoyang Li, Wei He, Wei Wu* School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA,Shanghai ，201200 ABSTRACT ：OBJECTIVE To preparebiotin-modified insulin liposomesand study the in vitro physicochemical properties, hypoglycemic effect and bioavailability in vivo, as well as the mechanism of enhanced oral absorption.METHODS Biotinylated liposomes containing synthetic biotin-DSPE was prepared using the reverse-phase evaporation technique. The formulation was optimized by particle size and entrapment efficiency. The transepithelial transport and cellular uptake was evaluated using Caco-2 cell model. The hypoglycemic effect and oral bioavailability in diabetic rats was investigated. RESULTS Optimized biotinylated liposomes improved transepithelial transport process and increased the cellular intake amount. The in vivo relativepharmacological bioavailability and bioavailability of insulin liposomes was 12.09% and 8.23%, respectively. RESULTS Liposomes modified with biotin could enhance the oral absorption of insulin by receptor-mediated endocytosis mechanism, showing such biotin- modified immunoliposomes may be a potential carrier for insulin oral delivery system. KEY