目的 制备阿齐他赛聚乙二醇单甲醚-聚乳酸双嵌段共聚物(mPEG-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 mV,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 aziditaxel-loaded mPEG-PLA polymeric micelles, investigate its pharmaceutical characteristics 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 micelles was observed under transmission electron microscope. The particle size distribution 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 loading and encapsulation efficiency were measured by HPLC. Dialysis method was used to investigate the in vitro release of aziditaxel-loaded micelles, and the release manner was fitted using the mathematic models. The in vitro anti-tumor activities were evaluated by proliferation inhibition and cycle block experiment. RESULTS Aziditaxel-loaded polymeric micelles were prepared successfully. Aziditaxel-loaded polymeric micelles showed spherical shape with a mean particle size of 24.50 nm, polydispersity index of 0.117 and Zeta potential of -10.06 mV. 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 reconstitution solution of lyophilized preparation of aziditaxel-loaded polymeric micelles maintained stable within 6 h. The release behavior of aziditaxel-loaded micelles conformed to the ambiexponent model. Drug-loaded micelles could obviously inhibit the proliferation of MCF-7 breast cancer cell lines in vitro, and induce significant G2/M cycle arrest and apoptosis on MCF-7 cancer cells. CONCLUSION Aziditaxel-loaded mPEG-PLA polymeric micelles are successfully prepared. The preparation method is simple, and the pharmaceutical properties of the products conform to the requirements of the subsequent study. The prepared aziditaxel-loaded polymeric micelles exhibit good application prospect with favourable in vitro anti-tumor activities.
关键词
阿齐他赛 /
胶束 /
载药量 /
释放 /
模型 /
抗肿瘤活性
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Key words
aziditaxel /
micelle /
drug loading /
release /
model /
anti-tumor activity
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中图分类号：
R944
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参考文献
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脚注
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基金
国家“重大新药创制”科技重大专项资助项目(2012ZX09301002-001-008)
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