近年来性传播已成为我国新发HIV感染的主要传播途径，通过药物实现HIV病毒暴露前预防显得尤为重要，其中多靶点联合用药的“鸡尾酒疗法”是艾滋病治疗中常用手段，这就对多药联合递送的阴道/直肠黏膜给药系统提出了需求，尤其需要解决亲、疏水性药物的有效控释问题。本课题拟构建适宜于阴道/直肠黏膜环境的聚阳离子温敏水凝胶，同时负载HIV-1病毒膜蛋白gp41融合肽抑制剂茶黄素双没食子酸酯TF-3和靶细胞辅助受体CCR5拮抗剂尼非韦罗，通过调控凝胶亲疏水微区和电荷密度，实现对亲水性药物TF-3和疏水性药物尼非韦罗的局部控制释放，提高药物的生物利用度并避免药物突释造成黏膜刺激；同时温敏凝胶对黏膜破损形成保护层，阻碍病毒与黏膜吸附，降低性传播感染HIV的风险。本项目通过对阳离子温敏水凝胶的结构性能与其黏膜给药功能性、生物安全性和阻断HIV感染效率的研究，为阻断HIV经性途径传播的杀微生物剂的开发提供可行途径。

In recent years, sexual transmission has become the major route of HIV infection in China, therefore, HIV pre-exposure prophylaxis by medications is particularly important. As the “cocktail therapy” has been commonly used in AIDS treatment, there comes the demands of multi-drug combined delivery for vaginal/rectal mucosa drug delivery system, especially the efficient controlled release of both hydrophobic and hydrophilic drugs. This research plans to develop polycation thermo-sensitive hydrogels which are suitable for vaginal/rectal mucosa drug delivery, meanwhile loading theaflavin-3,3'-digallate(TF-3) for blocking envelope glycoprotein gp41 of HIV-1 virus and nifeviroc as CCR5 receptor antagonist. By adjusting the hydrophilic/hydrophobic microdomains and charge density of these polycation thermo-sensitive hydrogels, the controlled release of hydrophilic TF-3 and hydrophobic nifeviroc in vagina/rectum is promisingly achieved. Thus bioavailability of both two drugs is enhanced and mucosal irritation can be avoided, in addition, hydrogel can form a protective layer on the surface of vaginal/rectal mucosa, prevent virus adsorption, and reduce the risk of sexually transmitted HIV infection. By research on stuctural performance, mucosal drug delivery ability, bio-safety and HIV blocking efficency of these polycation thermo-sensitive hydrogels, this project aims to provide feasible methods of microbicides development for HIV pre-exposure prophylaxis.