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

发布时间：2018-01-25 05:24

本文关键词： 阿齐他赛胶束载药量释放模型抗肿瘤活性　出处：《中国药学杂志》2015年19期 　论文类型：期刊论文

【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。
[Abstract]:Objective to prepare azetaxel poly (ethylene glycol) -poly (lactic acid) diblock copolymer (mPEG-PLA) polymer micelles. The physicochemical properties of drug-loaded micelles and their antitumor activities in vitro were investigated. Methods Acetaxel poly (ethylene glycol) -poly (lactic acid) diblock copolymer polymer micelles were prepared by thin-film dispersion method. The morphology of drug-loaded micelles was observed by transmission electron microscope, the particle size and Zeta potential of drug-loaded micelles were measured by laser particle size analyzer, and the reproducibility and resolubility stability of drug-loaded micelles were investigated. The drug loading and encapsulation efficiency of micelle were determined by HPLC. The release behavior of drug loaded micelle in vitro was investigated by dialysis, and the release curve was fitted by mathematical model. Proliferation inhibition assay and cycle arrest assay were used to evaluate the antitumor activity of Acetaxel in vitro. Results Acetaxel polymer micelles were successfully prepared in this experiment and their appearance was spherical. The particle size was 24.50 nm, the particle size multiple dispersion index was 0.117 渭 g Zeta potential was -10.06 MV, and the drug loading capacity was 16.00 卤0.15 渭 m 路mol ~ (-1) 路L ~ (-1) 路L ~ (-1) 路min ~ (-1). The entrapment efficiency was 95.80 卤0.10%, the preparation process was reproducible, the drug delivery micelle was stable within 6 h after resolution, and the release behavior of the drug carrier micelle in vitro was in accordance with the biphasic kinetic model. Drug carrier micelles could significantly inhibit the proliferation of MCF-7 breast cancer cells in vitro. The G _ 2 / M cycle arrest and apoptosis were induced in MCF-7 cells. Conclusion Acetaxel poly (ethylene glycol) -poly (lactic acid) diblock copolymer polymer micelles were prepared in this experiment. The micelle preparation process is simple and the physicochemical properties meet the requirements of follow-up studies. It has shown good antitumor effect in vitro and has a good application prospect.
【作者单位】：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;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;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;
【基金】：国家“重大新药创制”科技重大专项资助项目(2012ZX09301002-001-008)
【分类号】：R943;R96
【正文快照】： 紫杉醇和多西紫杉醇是目前较为有效的抗肿瘤药物,抗肿瘤谱广,临床上广泛用于乳腺癌和卵巢癌的治疗,但在临床使用过程中发现紫杉醇及多西紫杉醇对原发及继发性紫杉醇肿瘤耐药病人的化疗均无效,其重要原因之一就是患者肿瘤细胞中P-糖蛋白(P-gp)过度表达[1],导致药物外排增加,细

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