寡肽生物水凝胶用于蛋白药物定位输送与控释的研究

项目名称： 寡肽生物水凝胶用于蛋白药物定位输送与控释的研究

项目编号： No.81503012

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 姜天玥

作者单位： 南京工业大学

项目金额： 18.5万元

中文摘要： 针对蛋白药物输送系统的安全性、有效性以及药物稳定性等关键问题，本项目设计一类新型寡肽生物水凝胶，通过氨基酸生物小分子与生物大分子药物间的相容性高效包载蛋白，并以生物大分子酶为催化剂进行体外成胶，用于蛋白药物TRAIL的定位输送，控释药物，维持长效。本项目通过研究氨基酸类型、序列以及链长对成胶性的作用，酶的催化性能以及对蛋白活性的影响，研究水凝胶的体内外降解性、控制释放药物机制、对蛋白药物的输送性能等，阐明凝胶的结构与安全性、药物稳定性、成胶性、控释性等功能之间的规律，筛选出安全、高效的寡肽水凝胶作为蛋白药物递送的载体。探索基于生物分子氨基酸、酶、蛋白药物之间的作用机制，为蛋白药物的高效包载提供理论依据。这种基于全部以生物分子来构建递药系统的创新设计策略未见文献报道，为蛋白药物的输送提供了安全和高效的载体平台，并可推动蛋白药物的临床应用，也为其他生物大分子药物的输送提供实际可行的解决方案。

中文关键词： 蛋白药物；寡肽水凝胶；相容性；定位输送；控释

英文摘要： In view of the safety, effectiveness and stability of protein as the key issue in protein delivery system, a class of novel oligopeptide-based small-molecule hydrogels are developed for localized delivery of a protein drug, TRAIL, which gels in vitro by catalysis of biomacromolecular enzyme, presents high efficient protein-loading capacity based on the compatibility between small-biomolecular amino acids and biomacromolecular protein and shows controlled release of protein. In this project, the effect of type, sequence and length of amino acid on the gel-forming capacity as well as the catalytic activity of enzyme and its influence on the activity of protein drug are studied. The project is also focused on the in vitro and in vivo degradability, controlled drug release mechanism and protein delivery efficiency of hydrogel, which also explores the mechanism of interaction among biomolecules including amino acid, enzyme and protein drug for highly efficient protein efficiency. This new design for the drug delivery system composed of all biomolecules provides a safe and efficient platform for protein delivery and advances the application of protein in clinic, which also offers a practical carrier for delivery of other biomacromolecules.

英文关键词： Protein drug;Oligopeptide-based hydrogel;Compatibility;Localized delivery;Controlled release