多肽GRGDS修饰的紫杉醇长循环靶向脂质体的体外评价.doc

多肽GRGDS修饰的紫杉醇长循环靶向脂质体的体外评价( 赵 慧1，2，王坚成1，罗春蕾1，孙启时2，张 强1，3 (1 北京大学药学院药剂学系，北京 100083；2 沈阳药科大学中药学院，沈阳 110016； 3 北京大学天然药物与仿生药物国家重点实验室，北京 100083) [摘要] 目的：本研究以甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸 (glycine-arginine-glycine-aspartic acid-serine，GRGDS) 五肽修饰的脂质体作为抗癌药物-紫杉醇的载体，对其体外理化性质和细胞毒作用进行评价。方法：采用化学偶联合成DSPE-PEG-GRGDS，以此作为导向性材料，采用薄膜分散法制备载紫杉醇的PEG修饰长循环脂质体（GRGDS-SSL-PTX），并对脂质体的包封率、粒径和体外释放率等性质进行了考察，同时采用人卵巢癌SKOV-3细胞和人乳腺癌MCF-7细胞进行了体外细胞生长抑制的评价。结果：与普通紫杉醇长循环脂质体（SSL-PTX）相比，本研究所制备紫杉醇主动靶向脂质体（GRGDS-SSL-PTX）的粒径、包封率、载药量、体外释放及稳定性等理化性质无显著差异，包封率约为95%，平均粒径为（117.5±1.3）nm。冰冻蚀刻透射电镜观察结果表明，脂质体外观基本圆整且均匀分 散。体外释放结果表明，12 h内，分别有67.9%和72.3%的PTX从SSL-PTX和GRGDS-SSL-PTX中释放。体外细胞毒实验结果表明，GRGDS-SSL-PTX对人卵巢癌SKOV-3细胞和人乳腺癌MCF-7细胞的生长抑制作用均有增强，分别为SSL-PTX的1.42倍和2.12倍。结论： GRGDS 五肽修饰的紫杉醇靶向脂质体成功制备，将有利于体内肿瘤的靶向治疗效果。 [关键词] 整合素；脂质体；紫杉醇；靶向 [中图分类号] R943.42；R979.1 [文献标识码] A [文章编号] 1003-3734 In vitro evaluation of GRGDS peptide modified liposomes containing paclitaxel Zhao Hui1，2，Wang Jian-cheng1，Luo Chun-lei1，Sun Qi-shi2，Zhang Qiang1，3 （1 Department of Pharmaceutics，School of Pharmaceutical Sciences，Peking University，Beijing 100083，China；2 School of Traditional Chinese Medicine，Shenyang Pharmaceutical University，Shenyang 110016，China；3 The State Key Laboratory of Natural and Biomimetic Drugs，Peking University，Beijing 100083，China） [Abstract] Objective：To investigate the glycine-argine-glycine-aspartic acid-serine (GRGDS) modified liposomes as the carriers of anticancer drug-paclitaxel. Methods：The DSPE-PEG-GRGDS synthesized by DSPE-PEG-NHS and GRGDS was used as liposomes materials to obtain the paclitaxel loaded modified paclitaxel liposomes (GRGDS-SSL-PTX). The encapsulation efficiency，drug loading，particle size and in vitro release and cytotoxicity were performed. Results：The encapsulation efficiencies of the liposomes were above 95% and the modification of GRGDS didn’t affect the physicochemical characters，such as particle size，encapsulation efficiency and in vitro release. The average size of SSL-PTX and GRG