短肽衍生物自组装水凝胶的结构控制、刺激响应机理与药物缓控释研究

Supramolecular hydrogel based on the self-assembly of peptide is considered to be a very promising class of biofunctional materials because of its good biocompatibility, biodegradability and stimulate responsiveness.In this project, a series of peptide derivatives will be synthesized as gelators to produce supramolecular hydrogels through the molecular interaction. Anticancer drugs will be loaded in the self-assembling hydrogels. Firstly, peptide derivatives with sensitive functional groups will be synthesized through liquid phase method using amino acids condensation, and then self-assemble to form supramolecular hydrogel. The properties and biocompatility of hydrogel will be test. Change the gel self-assembly environment, such as temperature, pH, ionic strength, etc., to explore the micro-structure of gelator aggregates affected by the external environment and obtain the aggregates with structural controllability. Stimuli-responsive mechanism of the supramolecular hydrogel to the external environment will be studied in depth. The diffusion and release of anticancer drugs loaded in the hydrogel is closely related to the micro-structure, and this project will systematically research the controlled release mechanism of drugs in the different micro-structure hydrogels. This research will be significant to the design and preparation of novel drug delivery systems (DDS) for the controlled release of anticancer drugs, and its has potential applications in the field of life sciences.

短肽自组装水凝胶因其良好的生物相容性、生物降解性和刺激响应性而被认为是一类很有应用前景的生物功能材料。本项目采用液相法合成一系列带有敏感官能团的短肽衍生物作为凝胶剂，利用其在水中自组装制备超分子水凝胶并测试凝胶的基本性质。系统地研究凝胶剂的化学结构和自组装环境对凝胶聚集体微结构的影响，实现聚集体结构的可控。探讨短肽自组装水凝胶对外界环境(如温度、pH 值、离子强度等)的刺激响应机理，以及水凝胶的生物相容性，为其作为药物载体奠定基础。负载抗肿瘤药物分子于水凝胶体系中，系统地研究药物分子在凝胶体系内的扩散释放行为，探讨凝胶微结构对载药性质和体外释药性能的影响，明确短肽自组装水凝胶作为药物载体的构效关系。本项目在合成新型刺激响应性短肽衍生物的基础上，通过化学方法调控凝胶聚集体的微结构，进而控制药物分子的扩散释放，这些研究对新型抗肿瘤药物缓控释材料的设计和制备及其在生命科学领域的应用具有重要意义。

为了提高药物缓控释材料的生物相容性、生物降解性和刺激响应性，克服传统的聚合物水凝胶在这方面的缺陷，本项目合成了多种对环境具有响应性及良好生物相容性的树状大分子和化学修饰的天然高分子，以及选用市售的糖类衍生物作为凝胶剂，利用它们自组装形成超分子凝胶体系，并对基本凝胶性能（如凝胶化浓度、凝胶时间、凝胶-溶胶相转变温度等）进行了研究。探讨了水凝胶对外界环境（如温度、pH值、离子强度、CO2等）的刺激响应性，并对其响应机理进行了分析。通过体外细胞毒性实验测试了水凝胶的生物相容性；采用体内降解实验研究了水凝胶的生物降解性；研究了水凝胶的载药、释药性能，采用红外、荧光等多种手段研究了药物分子与水凝胶的相互作用机理，并对这些药物分子的体外释放动力学进行了研究。这些研究对新型药物缓控释材料的设计和制备及其在医学和生命科学领域的应用具有重要意义。