多肽GRGDS修饰的紫杉醇长循环靶向脂质体的体外评价  

In vitro evaluation of GRGDS peptide modified liposomes containing paclitaxel

作　　者：赵慧[1,2] 王坚成[1] 罗春蕾[1] 孙启时[2] 张强[1,3] 

机构地区：[1]北京大学药学院药剂学系,北京100191 [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,北京100191

出　　处：《中国新药杂志》2008年第23期2034-2038,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30572261);国家重大基础研究计划973项目(2007CB935801)

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,本研究制备的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(115.5±2.2)和(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。Objective： To investigate the glycine-argine-glycine-aspartic acid-serine （GRGDS） modified long circulating liposomes as the carriers of anticancer drug of paclitaxel. Methods：The DSPE-PEG-GRGDS synthesized by DSPE-PEG-NI-IS and GRGDS was used as liposome materials to obtain the paclitaxel loaded 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 showed no effect on the physicochemical characters, such as particle size, encapsulation efficiency and in vitro release. The average size of SSL-PTX and GRGDS-SSL-PTX were （115.5 ± 2.2）nm and （117.5 ± 1.3 ）nm respectively. The release of paclitaxel between the SSL-PTX and GRGDS-SSL-PTX within 12h has demonstrated to be 67.9% and 72.3%. In vitro cytotoxicities were increased by 1.42 fold in SKOV3 and 2.12 fold in MCF-7. Conclusion：GRGDS-SSL-PTX might be a potential formulation for targeting cancer therapy in patients.

关 键 词：整合素 脂质体 紫杉醇 靶向 

分 类 号：R943.42[医药卫生—药剂学] R979.1[医药卫生—药学]