基于自组装技术的新型载紫杉醇可控缓释PLGA基靶向复合微球的研究

项目名称： 基于自组装技术的新型载紫杉醇可控缓释PLGA基靶向复合微球的研究

项目编号： No.31200451

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 林学

项目作者： 王芳

作者单位： 南京林业大学

项目金额： 23万元

中文摘要： 紫杉醇是一种天然植物抗癌药物，临床使用时需在紫杉醇注射液中加入聚氧乙烯蓖麻油作为溶剂，但紫杉醇和聚氧乙烯蓖麻油均有较大毒性。采用纳米微球制备紫杉醇缓释剂可大大降低药物的毒副作用，具有重要的意义。本项目针对纳米缓释微球在药物释放初期存在的突释问题，基于天然多糖聚电解质的层层自组装技术，以生物降解高分子材料PLGA制备的载药纳米微球为模板，制备一种新型载紫杉醇可生物降解高分子复合微球，将叶酸连接到最外层表面，赋予载药微球对肿瘤细胞的主动靶向性。结合载体材料的降解机理，通过体外释放实验绘制不同影响因素下的释药曲线研究该体系的释药行为，对实验数据进行线性模拟，最终建立该体系的释药动力学方程，从而实现药物释放速率的可控性。研究成果可为可生物降解高分子载紫杉醇微球的临床应用提供依据。

中文关键词： 生物降解高分子；紫杉醇；自组装；缓控释微球；释药动力学

英文摘要： Paclitaxel is a natural efficient plant anti-tumor drug and the Cremorphor EL was used as the solvents of Paclitaxel in clinical, however both the solvent and paclitaxel have many side effects, such as causing severe allergic and toxicity reactions. Therefore, it is important to research the sustained release dosage form of Nano microspheres in order to reduce the side effects of drugs. In order to solve the burst release problem of drug delivery nanocapsules, in this project, a novel composite microsphere of paclitaxel carrier with a poly(D,L-lactide-co-glycolide)(PLGA) core will be fabricated, which is based on polyelectrolyte complexation of the natural polysaccharides prepared by the layer-by-layer approach, the surface of the composite microsphere will be connected to folate for the active target of tumor cells. Combined with the carrier material degradation mechanism, we will study the drug release behavior and get drug release curves of different influence factors through in vitro release experiment. Finally, we will do linear analog of the experimental data and establish drug release kinetics equation of the composite microspheres. The drug release kinetics equation will realize to control the drug release rate. Research results are very important for biodegradable polymer microspheres in the clinical ap

英文关键词： biodegrable polymer；paclitaxel；self-assembly；release microcapsule；drug release kinetics