Vaginal ring formulation of tenofovir microbicide

描述（由申请人提供）：本项目的长期目标是通过开发基于缓释释药的改进杀微生物剂，使妇女能够保护自己免受艾滋病毒感染。每天有15 000人受到感染，其中越来越多的是妇女。因此，开发一种有效的杀微生物剂对美国国立卫生研究院和其他世界卫生组织具有高度的方案相关性。目前已确定了60多种候选药物，其中18种已进入临床试验阶段。一个受到强烈关注的领域是阴道提供抗逆转录病毒药物。一项由NICHD和NIH其他研究所赞助的I期试验（HPTN 050）显示了替诺福韦凝胶制剂的耐受性。II期试验（HPTN 059）将进一步评估更大样本、更长时间的安全性和耐受性。目前还没有替诺福韦的缓释制剂在开发中。目前正在积极研究NNRTI T-120的阴道环配方，并显示出很大的希望。硅基给药平台的一个显著缺点是只能递送非常低溶解度的药物。我们已经开发了一种平台技术，可以通过植入来持续释放多种药物；抗病毒水平维持了很长时间。这项技术导致了更昔洛韦眼内植入物：Vitrasert。被批准用于治疗艾滋病相关巨细胞病毒性视网膜炎。我们建议利用这个平台开发替诺福韦的阴道环缓释制剂。该平台也可用于其他抗逆转录病毒药物，从而增加了相当于HAART的杀微生物剂的可行性。

DESCRIPTION (provided by applicant): The broad long term goal of this project is to empower women to protect themselves from HIV infection through the development of improved microbicides based on sustained release drug delivery. Each day 15,000 people are infected - a growing majority of them women. The development of an effective microbicide is thus of high programmatic relevance to the NIH as well as other world health organizations. There are more than 60 candidate agents identified, 18 of which have proceeded to clinical testing. One area that is receiving intense interest is the vaginal delivery of antiretroviral agents. A Phase I trial (HPTN 050), sponsored by the NICHD and other institutes of the NIH, showed tolerability of a gel formulation of tenofovir. A Phase II trial (HPTN 059) will further assess safety and tolerability in a larger sample for longer periods. There is currently no sustained release formulation for tenofovir in development. A vaginal ring formulation of the NNRTI T-120 is being actively investigated and shows great promise. A significant drawback of the silicone based delivery platform is that only very low solubility drugs can be delivered. We have developed a platform technology for the sustained release of a broad range of drugs by implantation; antiviral levels have been maintained for long periods. This technology lead to the ganciclovir intraocular implant: the Vitrasert., approved for the treatment of AIDS related CMV retinitis. We propose to utilize this platform to develop sustained release vaginal ring formulations for tenofovir. This platform could also be utilized for other antiretroviral agents, thus increasing the feasibility of a microbicide equivalent of HAART. PUBLIC HEALTH RELEVANCE: Each day 15,000 people are infected by HIV, the majority in sub-Saharan Africa and a growing percentage women infected though heterosexual sex. The broad long term goal of this project is to empower women to protect themselves from HIV infection through the development of an improved microbicide based on the sustained release drug delivery of the antiretroviral agent tenofovir.