具有嵌段接面交联结构的多功能药物载体研究

项目名称： 具有嵌段接面交联结构的多功能药物载体研究

项目编号： No.51203111

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机高分子材料学科

项目作者： 张玲

作者单位： 天津大学

项目金额： 25万元

中文摘要： 作为高分子药物载体的核交联及壳交联胶束分别具有药物承载率低及传送性能不佳等缺点。根据胶束的空间结构特性，对介于亲水段及疏水段间的"嵌段接面"进行交联，由于交联部位处于两亲性嵌段的中间部位，则可以改善核交联及壳交联结构的缺点，表现出更加优异的载体性能。本研究针对体内肿瘤的特点采用"嵌段接面"交联结构设计一种新型具有集成功能的药物载体：含有半乳糖基团的嵌段与在肿瘤环境（pH≈6.8）发生电荷反转的"二甲基马来酸修饰的丙烯酰胺"嵌段共同作为胶束外壳，使其成为可被肝癌细胞高效吸收的靶向药物载体；同时具有氧化还原开关响应性的可降解交联剂可以实现药物在细胞内的可控释放。本研究采用阿霉素作为靶药物，研究兼具靶向性、pH响应-电荷反转性、氧化还原开关响应性的新型药物载体，及其在不同"嵌段接面"结构条件下对载药量和药物可控性释放的影响规律，为高分子药物载体结构设计与性能的研究开拓新的方向。

中文关键词： 刺激响应性；电荷翻转；界面交联；还原敏感性；药物载体

英文摘要： Both core-crosslinked and shell-crosslinked micelles have disadvantages, such as low drug loading content and poor mobility, respectively. However, according to spatial structures of micelles, nexus-crosslinking, which happens between hydrophobic and hydrophilic blocks, should demonstrate overwhelming performance compared to the two crosslinking structures mentioned above. Aiming to design delivery carrier for a kind of typical anti-cancer drug, Doxorubicin, this project will focus on synthesis and analysis of aimed product, which presents combined multifunctional characteristics, including cancer cell targeting capability, charge-reversal capability, stimuli-responsibility as well as nexus-crosslinking structure. Nexus-crosslinking structure will be conducted resulting in high drug load and good mobility; blocks consisting of galactose moieties, which have been confirmed to target hepatocytese onto liver surface, will be introduced to present targeting capability; blocks grafted with dimethylmaleic acid can exhibit charge-conversion at tumor （pH≈6.8), which will enhance cellular uptake of delivery to solid tumors, via an adsorptive endocytotic pathway due to the electrostatic interaction between delivery and cells; reduction cleavable crosslinker will be used to lead to controlled release. Preparation and study

英文关键词： Stimuli-responsive；Charge Switchable；Interface-crosslinking；Reduction Responsive；Drug Delivery