刺激响应型超分子凝胶的设计组装及其药物控释研究

The self-assembling of small functional molecules into supramolecular structures is a powerful approach toward the development of new materials and new nanostructures. As a novel class of self-assembled materials, organogels have received considerable attention in recent years because their widely application prospects in the area of the drug controlled release for their easily modified structure, non-covalent intermolecular self-assembly and controllable micro-nano structures. This project aims to design and synthesize a series of organogelators by molecular design and chemical modification, combined with the specific structures of drug molecules, introduced appropriate functional groups to the gelator molecules, modulating the balance of hydrophilic and hydrophobic groups, constructed organogel materials suitble for loading of antibiotic drugs by supramolecular self-assembly. Further, we study on the reversible intelligent response prosess of the drug-loaded organogel to the site of lesion through the stimulation of heat or pH value in the modeling biological environment in vitro, monitor dynamic process of drug release through the specific signal groups in the gel, and provide the theory basis and application foundation as a guidance for design and synthesis with stimulus responsive drug release organogel materials. With the development of this project, it not only give the new methods for the design and synthesis of organogels and constructing the controllable organic nanometer materials, also can promote the application research for organogel used in antibiotic drug carrier materials,. At the same time, the research has important significance for people's health in reducing the use of antibiotic.

通过功能小分子的自组装形成功能集成的超分子结构在开发新材料和新结构方面具有重要的科学意义和实用价值。作为一类自组装材料，小分子水凝胶因其结构易修饰、非价键自组装及微纳结构可控性决定其在药物缓释载体领域的广阔应用前景。本项目旨在通过分子设计和化学修饰设计合成一系列超分子有机凝胶因子，结合负药物分子的特定结构，在分子中引入适当的功能基团，调节分子内亲疏水基团的结构平衡，利用超分子自组装构筑适合抗生素负载的小分子凝胶材料。研究载药凝胶在体外模拟生物环境中对病灶部位温度和pH值等信号的可逆智能响应,并通过凝胶分子内特定基团监控药物缓释的动态过程，为设计合成具有刺激响应性的药物缓释凝胶材料提供理论依据和应用基础。本项目的开展不仅为设计合成凝胶因子和构筑结构性能可控有机纳米材料提供新的方法，也可促进有机凝胶在抗生素类药物载体方面的应用研究，在减少抗生素使用、保障人类身体健康等方面具有重要意义。

设计合成了含有光响应性能的偶氮苯基团和共轭结构的邻菲罗啉基团的凝胶因子1，偶氮苯和邻菲罗啉基团以亲水性的酰胺基团相连接，偶氮苯基团尾端连接有疏水性能的烷氧基团。由于凝胶因子1的特殊结构，在分子内和分子间存在氢键作用，pi-pi相互作用和疏水作用等弱的相互作用力,凝胶因子1在溶液中对光表现出较好的响应性能。.设计合成了含有光响应性能的偶氮苯基团和疏水性能良好的胆甾醇基团的凝胶因子2，偶氮苯和胆甾醇基团之间以三枝状的柔性酰胺基团相连，同时酰胺基团也起到氢键连接基团的作用。在凝胶因子2中，由于分子内和分子间存在酰胺基团强烈氢键作用，偶氮苯基团间的pi-pi相互作用和胆甾醇基团的疏水作用等相互作用力。实验中，发现凝胶因子2在甲苯和环己烷溶剂中可以形成完全透明的稳定凝胶。凝胶因子2在环己烷和甲苯溶剂中形成稳定凝胶后，在外力的破坏作用下凝胶转变为溶液，溶液在经过静置较短一段时间后有可以重新转变为凝胶状态，表现出良好的自修复性能。.利用氧化还原法制备氧化石墨烯材料使其作为基底与有机荧光小分子产生能量共振转移作用，选用可特异性检测stDNA的荧光分子TO3-I作为荧光团，以共价键的形式把其嫁接到氧化石墨烯上。通过嫁接后的响应时间动力学、浓度滴定、选择性、检测限、材料粒径、Zeta电位和FESEM等，对荧光分子材料进行了分析。