多西他赛pH敏感嵌段共聚物胶束的备及其制剂学研究.docVIP

多西他赛pH敏感嵌段共聚物胶束的制备及其制剂学研究 陈大为*，鄢璐，乔明曦，胡海洋，赵秀丽，陈曦，邓意辉 （沈阳药科大学药学院药剂系，沈阳 110016） 摘 要：本文在合成pH敏感两亲性嵌段共聚物聚（2-乙基-2-噁唑啉）-聚乳酸（PEOz-PDLLA）的基础上，采用薄膜分散法制备了多西他赛pH敏感嵌段共聚物胶束，利用芘荧光探针技术测定胶束的临界胶束浓度（CMC）；通过高效液相色谱测定胶束的载药量及包封率；分别利用透射电镜、动态光散射法和Zeta电位分析仪对胶束的形态、粒径和表面电位进行了表征；采用透析法考察了载药聚合物胶束的体外释放行为。结果表明，胶束的临界胶束浓度值为1.0 ×10-3 g·L-1；载药量可达15.0%，包封率为91.1%；胶束具有很窄的粒度分布，平均粒径为28.7nm；胶束粒子为圆球形且分散良好，其表面Zeta电位值为（1.19±0.12）mV；在pH7.4释放介质中，多西他赛胶束具有缓释作用；而在pH5.0条件下，胶束释药明显加快，体现出PEOz-PDLLA胶束释药行为的pH敏感性。综合上述研究可见，PEOz-PDLLA嵌段共聚物胶束作为疏水性抗肿瘤药物的给药系统具有很好的应用前景。 关键词：多西他赛；pH敏感；嵌段共聚物；胶束；薄膜分散法 Preparation Study of docetaxel-loaded pH-sensitive block copolymer micelles CHEN Da-wei，YAN Lu ，QIAO Ming-xi，HU Hai-yang，ZHAO Xiu-li，CHEN Xi，DENG Yi-hui (Department of Pharmaceutics，School of Pharmaceutical Sciences，Shenyang Pharmaceutical University，Shenyang，110016，China) ABSTRACT: Basing on the synthesis of pH-sensitive amphiphilic block copolymer Poly(2- ethyl-2-oxazoline)-Poly(D,L-lactide)(PEOz-PDLLA), this paper prepared docetaxel-loaded pH-sensitive block copolymer micelles using film dispersion method. The Critical Micelle Concentration (CMC) was measured by Pyrene Fluorescent Probe Technique. The entrapment efficiency and drug-load amount were determined by HPLC. The morphology, diameter and surface potential of the micelles were characterized by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS) and Zeta potential analyzer, respectively. The in vitro release behavior of DTX from polymeric micelles was investigated using dialysis method. The results indicated that the CMC, drug-load amount and entrapment efficiency of the micelles was 1.0 ×10-3 g·L-1, 15.0% and 91.1%, respectively. The micelles had a narrow size distribution, with a mean diameter of 28.7nm. The micelle was globular-shaped and its Zeta potential was 1.19±0.12 mV. In pH 7.4 PBS, docetaxel was released in a sustained manner from the micelles; while in PBS at pH5.0, drug was released more rapidly, these results suggested the pH-sensitive drug