两亲性无规共聚物的设计、合成及靶向胶束行为研究

项目名称： 两亲性无规共聚物的设计、合成及靶向胶束行为研究

项目编号： No.20874086

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 武器工业

项目作者： 吴起

作者单位： 浙江大学

项目金额： 32万元

中文摘要： 本项目利用酶促选择性合成法制备了8种亲/疏水药物和4种糖的可聚合单体，并设计合成了一系列具有不同结构的无规共聚高分子药物。在此基础上，详细研究了两亲性无规高分子的胶束组装行为及其影响因素：首先以键合有糖-利巴韦林的两亲性无规共聚物为对象，考察其水相自组装能力，并测定临界聚集浓度、TEM形貌和流体力学直径，考察自组装条件、聚合物结构对组装影响，发现聚集体形貌的多样性，以及随时间的演化过程；此外，也以多种方式键合有疏水性酮洛芬的两亲性共聚物作为研究对象，比较考察其胶束组装行为和规律。在原计划基础上，也扩展考察键合有吉西他滨、5-氟胞苷、脱氧氟尿苷-阿糖胞苷双药体系等不同药物的两亲性共聚物的胶束组装行为，获得了对于无规共聚物组装性质和机理的较多认识。在构筑这些新型的功能化高分子药物胶束基础上，研究它们的药物缓释性和半乳糖基对ASGPR受体特异性识别的肝靶向特性，并通过聚合物结构的设计和调节来实现对组装胶束聚集体的形貌、缓释性、靶向性的有效调控。研究结果对于开发新型功能化的无规共聚高分子药物胶束、促进药物靶向控释系统研究发展都具有重要意义和应用前景。

中文关键词： 无规共聚物；胶束聚集体；靶向；缓释；合成。

英文摘要： In this project, we used selective enzymatic synthesis strategy to prepare polymerizable monomers of 8 hydrophilic/ hydrophobic drugs and 4 carbohydrates, and then designed a series of amphiphilic random copolymers with different structures. Furthermore, we investigated the micellization ability of these amphiphilic random copolymers: First, the amphiphilic random copolymers containing hydrophilic carbohydrate and ribavirin was used as the model, its micellization ability and CMC concentration, and morphology of the micelles were determined. The conditions for the micellization were optimized and the evolutionary process of the aggregates was observed successfully. Then, the micellization properties of several amphiphilic random copolymers containing hydrophobic ketoprofen and hydrophilic carbohydrate or PEG, which were prepared using different synthesis strategy, were compared. Moreover we also expanded the investigation of micellization using random copolymers containing different drugs such as gemcitabine, 5-Fluorocytidine, Floxuridine-cytarabine, some interesting results were obtained. Based on the synthesis of random copolymers and subsequent micellization, we investigated the drug controlled release, hepatoma-targeting and cytotoxicities, we also achieved the efficient control towards the morphology of micellization, release and targeting of the amphiphilic random copolymers systems. The results of this project were important for the development of novel micelle formed from functional amphiphilic random copolymers, and the research of drug controlled release.

英文关键词： random copolymers; micellization; targeting; controlled release; synthesis.