硬脂醇半乳糖苷修饰阿西替尼脂质体的制备及体外细胞毒性研究

发布时间：2018-06-12 08:05

  本文选题：阿西替尼 + 脂质体　； 参考：《中国新药杂志》2017年03期

【摘要】：目的:研究硬脂醇半乳糖苷修饰的阿西替尼脂质体对人肝癌SMMC-7721细胞株的增殖及凋亡的诱导作用。方法:采用冷冻干燥法制备硬脂醇半乳糖苷修饰的阿西替尼脂质体,以包封率为评价指标,采用葡聚糖凝胶过滤法和高效液相色谱法测定硬脂醇半乳糖苷修饰的阿西替尼脂质体的包封率。采用Box-Behnken响应面设计法优化制备工艺,并研究CCK-8法检测硬脂醇半乳糖苷修饰的阿西替尼脂质体对人肝癌SMMC-7721细胞株的抑制情况,采用Annexin V/PI流式细胞分析法检测细胞凋亡,Western blot检测凋亡蛋白Bax,Bcl-2,P53的表达。结果:最佳工艺:药脂比为1∶20,胆脂比为1∶8,硬脂醇半乳糖苷与磷脂比为1∶15,水合温度为55℃。CCK-8法检测不同浓度的硬脂醇半乳糖苷修饰的阿西替尼脂质体对SMMC-7721细胞株的增殖具有抑制作用,呈现时间和浓度依赖性。Annexin V/PI流式细胞分析法检测硬脂醇半乳糖苷修饰的阿西替尼脂质体对人肝癌SMMC-7721细胞株的抑制率优于人肺癌A549细胞株,Western blot检测发现随着硬脂醇半乳糖苷修饰的阿西替尼脂质体浓度的升高,Bax,P53蛋白的表达逐渐升高,Bcl-2蛋白的表达逐渐降低。结论:硬脂醇半乳糖苷修饰的阿西替尼脂质体在一定浓度范围内,可在体外抑制人肝癌SMMC-7721细胞株的增殖并诱导其凋亡,且随着硬脂醇半乳糖苷修饰的阿西替尼前体脂质体的浓度升高,凋亡率显著增加,可能的机制是增强促凋亡蛋白Bax,P53的表达,降低抗凋亡蛋白Bal-2的表达。硬脂醇半乳糖苷修饰的阿西替尼脂质体诱导SMMC-7721细胞株凋亡能力比A549强,初步判定硬脂醇半乳糖苷修饰的阿西替尼脂质体具有主动肝靶向性。
[Abstract]:Aim: to investigate the induction of apoptosis and proliferation of human hepatoma cell line SMMC-7721 by stearic galactoside modified acitinib liposome. Methods: stearol galactoside modified acitinib liposomes were prepared by freeze-drying method. The entrapment efficiency of acetinib liposomes modified with stearic galactoside was determined by dextran gel filtration and high performance liquid chromatography. The preparation process was optimized by Box-Behnken response surface design, and the inhibition of acitinib liposomes modified with stearin on human hepatoma cell line SMMC-7721 was studied by CCK-8 method. The expression of apoptotic protein Bax-Bcl-2 and p53 was detected by Annexin V / Pi flow cytometry and Western blot. Results: the optimum conditions were as follows: the ratio of stearin to lipid was 1: 20, the ratio of gallbladder to lipid was 1: 8, the ratio of stearol galactoside to phospholipid was 1: 15, and the hydration temperature was 55 鈩，

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