积极寻找和研发新型促渗剂，对我国药物经皮递送系统的发展具有重要意义。我们的前期工作证明了离子液体显著的经皮促渗活性，但是皮肤安全性问题制约了其在经皮给药系统中的进一步应用。本项目拟结合离子液体的经皮促渗活性，制备兼有生物降解特性和可设计性的新型氨基酸酯类离子液体，并进行促渗机制研究。项目将重点开展以下两方面的工作：第一，以天然氨基酸为原料，制备生物可降解离子液体，对其经皮促渗活性展开构效关系研究，明确该类化合物促渗活性与特征结构之间的关系，在此基础上进行分子结构优化，以安全和高效为导向，设计新型离子液体促渗剂；第二，从皮肤屏障功能出发，深入探索该类促渗剂对皮肤结构特征的影响、与角蛋白的结合作用以及对皮肤屏障功能相关因子的调控，从三个层面阐述该类促渗剂经皮促渗活性的作用机制。本项目的研究成果将推动离子液体在医药领域的进一步应用和发展，为我国经皮给药系统的开发和设计提供新的研究思路。

Skin penetration enhancers (PE) are one of the most important components in transdermal drug delivery system (TDDS). Screening and designing novel PE are significance for TDDS industry development. Our previous works have shown the enhancements of ionic liquids (ILs) on drug percutaneous absorption, but the safety issues limit the further application of ILs in TDDS. Hence, the aims of this work are to develop novel ILs from amino acid esters with both skin permeability and biodegradability, and investigate the mechanism of the promotion activities. First, we will prepare amino acid ester type-ILs ([AAE]X) and explore the inherent relationship between structures of ILs and their promotion activities by means of Quantitative Structure-Activity Relationship (QSAR) study. Based upon the results of QSAR, we will design novel PE from [AAE]X under structure optimization. Second, we will deeply investigate the influences of ILs on skin permeability. To achieve this goal, the influence of [AAE]X on skin properties, the interactions of compound-keratin and the moderation on expression of skin barrier agent properties will be deeply studied.at issue, cell and molecular levels to clarify the permeation mechanism. The achievements of this work will promote the further application and developments of ILs in medicine fields, and afford new approaches for the design and preparation of novel TDDS.