载阿齐他赛聚乙二醇单甲醚-聚乳酸双嵌段共聚物纳米胶束的制备、表征及体外抗肿瘤活性的研究  

Preparation,Pharmaceutical Characterization and in Vitro Anti-tumor Effects of Aziditaxel-loaded m PEGPLA Micelles

作　　者：陈丽青[1,2] 黄伟[1,2] 高钟镐[1,2] 方唯硕[1,3] 金明姬 

机构地区：[1]中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室,北京100050 [2]中国医学科学院北京协和医学院药物研究所药物研究所药物制剂研究室,北京100050 [3]中国医学科学院北京协和医学院药物研究所天然药物化学研究室,北京100050

出　　处：《中国药学杂志》2015年第19期1688-1695,共8页Chinese Pharmaceutical Journal

基　　金：国家“重大新药创制”科技重大专项资助项目(2012ZX09301002-001-008)

摘　　要：目的制备阿齐他赛聚乙二醇单甲醚-聚乳酸双嵌段共聚物(m PEG-PLA)聚合物胶束,考察载药胶束的理化性质并研究其体外抗肿瘤活性。方法采用薄膜分散法制备阿齐他赛聚乙二醇单甲醚-聚乳酸双嵌段共聚物聚合物胶束,透射电镜观察载药胶束的形态,激光粒度分析仪测定载药胶束的粒径和Zeta电位,考察载药胶束的工艺重现性和复溶稳定性,HPLC测定胶束载药量和包封率,透析法考察载药胶束的体外释放行为,并对释放曲线进行数学模型拟合,增殖抑制实验和周期阻滞实验评价其体外抗MCF-7肿瘤细胞活性。结果本实验成功制备了阿齐他赛聚合物胶束,其外观形态呈球形,粒径为24.50 nm,粒径多分散指数为0.117,Zeta电位为-10.06 m V,载药量为(16.00±0.15)%,包封率为(95.80±0.10)%,制备工艺重现性良好,载药胶束冻干制剂复溶后6 h之内保持稳定,载药胶束体外释放行为符合双相动力学模型,载药胶束在体外能明显抑制MCF-7乳腺癌细胞的增殖,并诱导MCF-7细胞产生明显的G2/M周期阻滞和细胞凋亡。结论本实验制备了阿齐他赛聚乙二醇单甲醚-聚乳酸双嵌段共聚物聚合物胶束,胶束制备工艺简单,理化性质符合后续研究要求,在体外显示了良好的抗肿瘤作用,具有良好应用前景。OBJECTIVE To prepare aziditaxel-loaded mPEG-PLA polymeric micelles, investigate its pharmaceutical characteris- ties and study its anti-tumor effects in vitro. METHODS Aziditaxel-loaded polymeric micelles were prepared by thin-film dispersion method. The morphology of aziditaxel-loaded mieelles was observed under transmission electron microscope. The partMe size distribu- tion and Zeta potential of aziditaxel-loaded micelles were determined by dynamic light scattering method using a Malvern Zetasizer Nano ZS90 analyzer. The technical reproducibility and reconstitution stability of aziditaxel-loaded micelles were also checked. The drug load- ing and encapsulation efficieney were measured by HPLC. Dialysis method was used to investigate the in vitro release of aziditaxel-load- ed mieelles, and the release manner was fitted using the mathematic models. The in vitro anti-treMor activities were evaluated by prolif- eration inhibition and cycle block experiment. RESULTS Aziditaxel-loaded polymeric micelles were prepared suceessfully. Aziditax- el-loaded polymeric mieelles showed spherical shape with a mean particle size of 24. 50 nm, polydispersity index of 0. 117 and Zeta po- te.ntial of - 10. 06 inV. The mean drug loading and entrapment efficiency were （ 16. 00 ±0. 15 ） % and （95.80 ± 0. 10） %, respectively. The preparation reproducibility was fine, and the reeonstitution solution of lynphilized preparation of aziditaxel-loaded polymeric mieelles maintained stable within 6 h. The release behavior of aziditaxel-loaded micelles conformed to the ambiexponent model. Drug-loaded mi- eelles couht obviously inhibit the proliferation of MCF-7 breast cancer cell lines in vitro, and induce significant G2/M cycle arrest and ap- optosis on MCF-7 cancer cells. CONCLUSION Aziditaxel-luaded mPEG-PLA polymeric micelles are successfully prepared. The prepa- ration method is simple, and the pharmaceutical properties of the products conform to the requirements of the subsequent study. The pre- pared aziditaxel-loaded polynler

关 键 词：阿齐他赛 胶束 载药量 释放 模型 抗肿瘤活性 

分 类 号：R944[医药卫生—药剂学]