Y型糖核异臂两亲性脂肪族聚酯/聚乙二醇星形聚合物的酶促合成及其拓扑结构与性能的关系

项目名称： Y型糖核异臂两亲性脂肪族聚酯/聚乙二醇星形聚合物的酶促合成及其拓扑结构与性能的关系

项目编号： No.51273123

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 汪秀丽

作者单位： 四川大学

项目金额： 79万元

中文摘要： 两亲性星形聚合物由于其独特的拓扑结构在自组装形貌控制以及作为药物释载体方面比线性聚合物更具有优势。本项目拟以聚对二氧环己酮（PPDO）、聚乙二醇（PEG）、聚（ε-己内酯）（PCL）及其它们的嵌段共聚物为臂，以烷基吡喃葡糖苷为核，利用酶催化的高度立体及区域选择性，无需保护及脱保护步骤就可以合成出具有Y型结构、可完全生物降解、生物相容的两亲性糖核脂肪族聚酯/聚乙二醇星形聚合物。利用两亲性星形共聚物溶解性的差别及微相分离可以获得不同形貌的纳米聚集体。由于糖核的引入，此类星形聚合物形成的纳米载药胶束还具有特异性细胞识别的功能。本项目将详细研究所合成的星形聚合物的拓扑结构与其性能、自组装行为的内在联系，为该类糖核异臂星形聚合物在药物控释领域的应用奠定理论基础。通过对酶促合成星形聚合物的研究，将拓宽酶催化在合成高分子中的应用，并为获得无金属残留的、更适应生物医用的星形聚合物提供新方法。

中文关键词： 星形聚合物；糖核；脂肪族聚酯；酶催化；药物载体

英文摘要： Many amphiphilic copolymers based on aliphatic polyesters such as poly(ε-caprolactone) (PCL) and poly(p-dioxanone) (PPDO) and poly(ethylene glycol) (PEG), which is one of the most widely used hydrophilic polymers have been synthesized as hydrophobic drug carriers. Because these amphiphilic copolymers can self assemble into nanometric micelles in aqueous solution, they can escape from reticuloendothelial system (RES). It was well known that the topological structure has great relationship with the morphology, stability and the size of micelle, which will directly decide the drug capacity, drug release and in vivo circulation. Recently many literatures demonstrated that star polymers have advantages in self-assembled morphology control as well as drug release compared to the linear polymer. In this project,Y type 3-miktoarm star copolymers will be synthesized by enzyme in which PCL, PPDO and PEG as well as their copolymers are arms, alkyl α-D-glucopyranoside is a core. Due to the high regioselectivity and stereoselectivity of enzyme catalysis, no protection and de-protection procedures will be needed. Firstly, sugar containing PPDO (sugar-P) will be synthesized by enzyme catalyzed ring-opening polymerization (EROP) of p-dioxanone (PDO) specifically initiated by the 6-primary alcohol of alkyl α-D-glucopyranoside.

英文关键词： star copolymers；sugar-core；aliphatic polyester；enzymatic catalysis；drug carriers