载多西紫杉醇脂质微泡对人肝癌HepG2细胞抑制作用的体外研究

目的：观察自制载多西紫杉醇脂质微泡联合超声对人肝癌HepG2细胞的抑制作用。方法：通过薄膜分散法制备载多西紫杉醇脂质微泡,观察其形态,测定粒径大小、包封率、载药量及稳定性等性质;将人肝癌HepG2细胞随机分为5组,对照组、多西紫杉醇组（DOC组）、多西紫杉醇联合超声组（DOC＋US组）、载多西紫杉醇脂质微泡组（DLLM组）、载多西紫杉醇脂质微泡联合超声组（DLLM＋US组）,CCK-8法检测细胞毒性,倒置显微镜观察细胞凋亡的形态,DAPI荧光染色法观察凋亡细胞核的改变。结果：载多西紫杉醇脂质微泡形态光滑圆整,无黏连;粒径分布范围为170~590 nm,平均粒径为350 nm;Zeta电位为-5.2 mV;微泡的包封率为80.0%,载药量为18.5%;4℃条件下保存14天性质稳定;DLLM＋US组较其他各组对肿瘤细胞有更为明显的抑制增殖及诱导凋亡效应（P〈0.01）。结论：自制载多西紫杉醇脂质微泡粒径小,包封率高,稳定性好,此微泡联合超声对人肝癌HepG2细胞有明显抑制作用,载多西紫杉醇脂质微泡有望成为一种新型抗肿瘤给药途径。

Effects of Docetaxel-Loaded Lipid Microbubblesand on Human Hepatocellular Carcinoma HepG2 Cell

Objective： To investigate the inhibition effects of in-house docetaxel-loaded lipid microbubbles（DLLM） combine with ultrasound（US） on human hepatocellular carcinoma HepG2 cell were measured in vitro. Methods： DLLM Wereas prepared by film dispersion, method, the shape of DLLM was observed and its properties were measured including particle size, encapsulation efficiency,drug loading and stability, and its physical properties were characterized; HepG2 cell strain were randomly divided into 5 groups： control group, docetaxel group（DOC group）, docetaxel combined with ultrasound group（DOC＋US group）, docetaxel-loaded lipid microbubbles（DLLM group）, docetaxel-loaded lipid microbubbles combine with ultrasound group（DLLM＋US group）, cytotoxicity was evaluated by CCK-8 assay, and the shape of cell apoptosis was observed by inverted microscope, and the variation in apoptotic nuclei was observed by DAPI fluorescent staining. Results： The in-house DLLM wereas found to be smooth and rounded without adhesion,The size distribution ranges between 170nm and 590nm,With a mean diameter of 350nm, and the zeta potential was measured to be-5.2 mV; Drug entrapment efficiency was 80.0 % and drug-loading amount was 18.5 %.DLLM is stable under the condition of 4 ℃ for 14 day. The tumoricidal activity and apoptosis induction of DLLM＋US group was significantly greater than that in other groups（P0.01）. Conclusion： The in-house DLLM with small particle size, high encapsulation efficiency, good stability,DLLM combine with ultrasound can inhibite the growth of human hepatocellular carcinoma HepG2 cell, DLLM could become a new drug delivery system for anti-tumor application.