Vaginal ring formulation of tenofovir microbicide

替诺福韦杀菌剂阴道环制剂

• 批准号: 7417412
• 负责人: Thomas J. Smith
• 金额: $ 15.35万
• 依托单位: OAK CREST INSTITUTE OF SCIENCE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7417412
• 关键词: Acquired Immunodeficiency Syndrome; Africa South of the Sahara; Animal Model; Animals; Anti-Retroviral Agents; Antiviral Agents; Area; Buffers; Characteristics; Cytomegalovirus Retinitis; Development; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Economic Development; Employee; Foundations; Ganciclovir; Gel; Goals; HIV; HIV Infections; Heterosexuals; Highly Active Antiretroviral Therapy; Implant; Institutes; Knowledge; Lead; Legal patent; Marketing; Modeling; National Institute of Child Health and Human Development; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Process; Production; Recording of previous events; Reporting; Research; Research Personnel; Risk; SIV; Safety; Sampling; Science; Services; Silicones; Solubility; System; Technology; Tenofovir; Testing; United States National Institutes of Health; Vaginal Ring; Vaginal delivery procedure; Water; Woman; World Health Organization; base; drug distribution; efficacy testing; empowered; high risk; implantation; improved; in vitro testing; in vivo; innovation; interest; microbicide; non-nucleoside reverse transcriptase inhibitors; novel; programs; public health relevance; research and development; research clinical testing; sex; transmission process; volunteer

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.

描述（由申请人提供）：该项目的广泛长期目标是通过开发基于缓释药物递送的改进的杀微生物剂，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，其中越来越多的人是妇女。因此，开发一种有效的杀微生物剂对美国国立卫生研究院以及其他世界卫生组织具有高度的规划意义。目前已确定了60多种候选药剂，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抗逆转录病毒药物的阴道给药。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。一项II期试验（HPTN 059）将在更大的样本中进一步评估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。NNRTI T-120的阴道环制剂正在积极研究中，并显示出很大的前景。基于硅酮的递送平台的显著缺点是只能递送溶解度非常低的药物。我们开发了一种通过植入持续释放多种药物的平台技术;抗病毒水平长期保持不变。这项技术导致更昔洛韦眼内植入物：Vitrasert。被批准用于治疗艾滋病相关的CMV视网膜炎。我们建议利用这个平台开发替诺福韦阴道环缓释制剂。该平台也可用于其他抗逆转录病毒药物，从而增加了高效抗逆转录病毒疗法等效杀微生物剂的可行性。 公共卫生关系：每天有15 000人感染艾滋病毒，大多数在撒哈拉以南非洲，越来越多的妇女通过异性性行为感染。该项目的广泛的长期目标是，通过开发一种基于抗逆转录病毒药物替诺福韦缓释给药的改良杀微生物剂，增强妇女保护自己免受艾滋病毒感染的能力。