抗肿瘤药H6聚合物胶束的制备及体外抗肿瘤作用研究

Study on Preparation of Anti-tumor Drug H6 Polymeric Micelles and Their in vitro Anti-tumor Effects

目的:制备抗肿瘤药H6(内酯类化合物)聚合物胶束,考察其体外抗肿瘤作用。方法:以甲氧基聚乙二醇-聚(ε-己内酯)(m PEG_(2000)-PCL_(4000))为载药材料,制备H6/m PEG_(2000)-PCL_(4000)胶束。以粒径、多分散系数(PDI)和48 h是否产生沉淀为指标筛选处方投料比、H6质量浓度、有机溶剂体积比,检测所制胶束的包封率和载药量。采用MTT法检测所制胶束与H6溶液对人非小细胞肺癌细胞A549、人肺癌细胞H460的毒性。结果:确定处方为投料比为1∶25、H6质量浓度为2 mg/m L、乙醇-氯仿为1∶1(V/V);所制备的H6/m PEG_(2000)-PCL_(4000)胶束的粒径为(40.74±0.116 3)nm,PDI为0.101±0.006,包封率为(94.87±0.016 3)%,载药量为(7.07±0.001 5)%(n=3)。胶束和H6溶液对A549细胞的IC_(50)分别为15.62、12.57 nmol/L,对H460细胞的IC_(50)分别为27.68、15.19 nmol/L。结论:成功制得H6/m PEG_(2000)-PCL_(4000)胶束,其具有体外抗肿瘤作用。

OBJECTIVE： To prepare anti-tumor drug H6 （lactone compound） polymeric micelles, and to investigate its in vitro anti-tumor effects. METHODS： Using mPEG2000-PCL4000 as carrier, H6/mPEG2000-PCL4000 micelles were prepared. Using particle size, PDI and 48 h whether to produce precipitation as indexes, feeding ratio, H6 concentration, volume ratio of organic solvent were screened. The encapsulation efficiency and drug-loading amount of micelle were all detected. MTT assay was used to detect the tox-icity of micelles and H6 solution to human non-small cell lung cancer cell A549 and human lung cancer cell H460. RESULTS： The screened formulation was as follows as feeding ratio of 1 ： 25, H6 concentration of 2 mg/mL, the ratio of ethanol to chloroform of 1 ： 1 （V/V）. The parameters of prepared H6/mPEG2000-PCL4000 micelles were as follows as particle size of （40.74 ± 0.116 3） nm, PD1 of （0.101± 0.006）, encapsulation efficiency of （94.87 ±0.016 3）%, drug-loading amount of （7.07 ± 0.001 5）% （n=3）. IC50 of mi- celles and H6 solution to A549 cell were 15.62 and 12.57 nmol/L; IC50 of micelles and H6 solution to H460 cell were 27.68 and 15.19 nmol/L. CONCLUSIONS： H6/mPEG2000-PCL4000 micelles are prepared successfully and show in vitro anti-tumor effects.