紫杉醇的聚(2-乙基-2-噁唑啉)-维生素E琥珀酸酯pH敏感聚合物胶束的制备与体外表征

摘要

为了确保将抗肿瘤药物递送到肿瘤部位并在肿瘤细胞内快速释药,本研究设计并制备了包载紫杉醇(PTX)的聚(2-乙基-2-噁唑啉)-维生素E琥珀酸酯(PEOz-VES) pH敏感聚合物胶束.用1H NMR确证了所合成的PEOz-VES的结构,用GPC测定其分子量为1212 g/mol,酸碱滴定法测定其pKa为6.01,芘荧光探针法测定其临界胶束浓度为(5.84士0.02) mg/L.采用薄膜水化法制备包载PTX的PEOz-VES胶束,载药量和包封率分别为(2.63士0.16)％和(84.1±3.38)％.动态光散射法测得胶束的粒径约为30 nm,Zeta电势为4.86 mV.TEM显示胶束呈均匀的球形.体外释放结果表明,PEOz-VES胶束具有pH依赖性释放行为,随着pH降低胶束的释放逐渐加快.因此该胶束可以识别正常组织和肿瘤组织间的pH差异并能响应胞内的pH梯度,预示该胶束具有肿瘤靶向性和胞内快速释药的特征,是一种较有潜力的抗肿瘤药物递送载体.%To ensure the delivery of antitumor drugs to tumor site and quick release in tumor cells,we designed and prepared pH-sensitive polymeric micelles by combining cationic ring-opening polymerization of 2-ethyl-2-oxazoline (EOz) with vitamin E succinate (VES),and then encapsulating paclitaxel (PTX) into the micelles self-assembled by poly(2-ethyl-2-oxazoline)-vitamin E succinate (PEOz-VES).The structure of the synthesized PEOz-VES was confirmed by 1H NMR spectrum,and the molecular weight measured by GPC was 1212 g/mol.The pKa of PEOz-VES with a low critical micelle concentration of (5.84±0.02) mg/Lwas determined to be 6.01.The PTX-loaded PEOz-VES polymeric micelles prepared by film hydration method were characterized to have a nanoscaled size of about 30 nm in diameter,a positive Zeta potential of 4.86 mV and uniform spherical morphology by TEM observation.The drug loading content and encapsulation efficiency were (2.63±0.16)％ and (84.1+3.38)％,respectively.The in vitro release behavior of PTX from PEOz-VES rnicelles in PBS displayed pH-dependent pattern and was gradually accelerated with decrease of pH value,implying that the micelles could distinguish endo/lysosomal pH and tumor extracellular pH from physiological pH by accelerating drug release.Therefore,the designed PEOz-VES micelles might have significant promise for anti-cancer drug delivery.