ZS1肽修饰共载紫杉醇和姜黄素脂质体的构建及其体外靶向性和毒性

Preparation, in vitro Targeting Effect and Cytotoxicity of Paclitaxel and Curcumin Co-loaded Liposomes Decorated with ZS1 Peptide

采用薄膜分散法制备的ZS1肽修饰共载紫杉醇(1)和姜黄素(2)的脂质体平均粒径为(92.8±3.5)nm,ζ电位为(13.50±2.55)mV。脂质体对1和2的包封率为84.5%和75.6%。脂质体在含50%胎牛血清的磷酸盐缓冲液(pH 7.4)中孵育24 h,透光率未发生明显变化,提示制品在血清中稳定性较好。体外细胞摄取试验表明,A549肺癌细胞对ZS1肽修饰脂质体的摄取效率是未修饰脂质体的3.3倍;而人脐静脉内皮细胞株(HUVEC)对两种脂质体的摄取效率相当,提示ZS1肽修饰可使脂质体具有潜在的主动靶向于A549肺癌细胞作用。细胞毒性试验结果显示,空白脂质体对A549肺癌细胞无明显细胞毒性,ZS1肽修饰共载脂质体、ZS1肽修饰1脂质体、ZS1肽修饰2脂质体及未修饰的共载药脂质体的细胞存活率分别为11%、36%、51%和61%。

The ZS1 peptide decorated liposomes loaded with paclitaxel （1） and curcumin （2） were prepared by thin film hydration method. The particle size and ζ potential of the product were （92.8±3.5） nm and （13.50±2.55） mV. The entrapment efficiency of I and 2 were 84.5 % and 75.6 %. The transmittance values of the product after incubation with phosphate buffer containing 50 % fetal bovine serum for 24 h were not significantly changed, which indicated the prepared liposomes were rather stable in serum. The results of in vitro uptake test showed that the cellular uptake efficiency of the ZS1 peptide decorated liposomes by A549 ceils was 3.3 times higher than that of the unmodified liposomes, while the uptake efficiencies of both liposomes by human umbilical vein endothelial cells （HUVEC） were close. It indicated that the liposomes decorated with ZS 1 peptide had a potential effect of active targeting to A549 cells. The blank liposomes had no cytotoxicity on A549 cells. The cell viabilities of the title liposomes, ZS 1-modified liposomes loaded with 1 or 2 and the unmodified liposomes were 11%, 36 %, 51% and 61%, respectively.