Preparation and in vitro characterization of paclitaxel-loaded pH-responsive polymeric micelles based on poly(2-ethyl-2-oxazoline)-vitamin E succinate  

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（英文）

作　　者：屈小又 邹洋 靳尧 周远航 王子琪 何楚瑜 邓运强 李馨儒 周艳霞 刘艳 

机构地区：[1]北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2017年第8期582-588,共7页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.81673366);the National Key Science Research Program of China(973 Program,Grant No.2015CB932100)

摘　　要：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/L was 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 micelles 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.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)p H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p Ka为6.01,芘荧光探针法测定其临界胶束浓度为(5.84±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±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 m V。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p H依赖性释放行为,随着p H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p H差异并能响应胞内的p H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。

关 键 词：Polymeric micelles pH-Responsibility Poly（2-ethyl-2-oxazoline） PACLITAXEL In vitro release 

分 类 号：R943[医药卫生—药剂学]