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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: In this study, a liposome modified with glycine-arginine-glycine-aspartic acid-serine (GRGDS) pentapeptide was used as a carrier of anticancer drug-paclitaxel. Its physical and chemical properties and cytotoxicity were evaluated. METHODS: DSPE-PEG-GRGDS was synthesized by chemical coupling as guide material. PEG-modified long-circulating liposomes containing paclitaxel (GRGDS-SSL-PTX) were prepared by membrane dispersion method. Blocking rate, particle size and in vitro release rate were investigated. In addition, human ovarian cancer SKOV-3 cells and human breast cancer MCF-7 cells were used to evaluate the in vitro cell growth inhibition. Results: Compared with SSL-PTX, the particle size, encapsulation efficiency, drug loading and release in vitro of paclitaxel active targeted liposomes (GRGDS-SSL-PTX) There was no significant difference in physico-chemical properties such as stability and entrapment efficiency. The entrapment efficiency was about 95% and the average particle size was (115.5 ± 2.2) and (117.5 ± 1.3) nm. The freeze-etched TEM observations showed that the liposomes were substantially round in appearance and uniformly dispersed. In vitro release results showed that 67.9% and 72.3% of PTX were released from SSL-PTX and GRGDS-SSL-PTX within 12 h, respectively. The results of in vitro cytotoxicity showed that GRGDS-SSL-PTX enhanced the growth inhibition of human ovarian cancer cell line SKOV-3 and human breast cancer cell line MCF-7 by 1.42-fold and 2.12-fold, respectively. Conclusion: The successful preparation of paclitaxel-targeted liposome modified with GRGDS pentapeptide will be beneficial to the targeted therapy of tumors in vivo.