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)：该项目广泛的长期目标是通过开发基于缓释药物传递的改进的杀微生物剂来增强妇女保护自己免受艾滋病毒感染的能力。每天有15,000人感染--其中越来越多的是女性。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很高的方案相关性。已确定的候选药物有60多种，其中18种已进入临床试验。引起人们强烈兴趣的一个领域是抗逆转录病毒药物的阴道给药。由NICHD和美国国立卫生研究院其他研究所赞助的一项I期试验(HPTN 050)显示，替诺福韦凝胶制剂是耐受性的。第二阶段试验(HPTN 059)将在更长时间内的更大样本中进一步评估安全性和耐受性。目前尚无正在开发中的替诺福韦缓释制剂。NNRTI T-120的一种阴道环配方正在积极研究中，并显示出巨大的前景。基于硅胶的给药平台的一个显著缺点是只能给药非常低的溶解度。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；抗病毒水平已经保持了很长时间。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的CMV视网膜炎。我们建议利用这一平台来开发替诺福韦的缓释阴道环制剂。该平台还可以用于其他抗逆转录病毒药物，从而增加了等同于HAART的杀微生物剂的可行性。 与公共卫生相关：每天有15,000人感染艾滋病毒，其中大多数在撒哈拉以南非洲，通过异性性行为感染的妇女比例越来越高。该项目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药物的改良杀微生物剂，使妇女能够保护自己免受艾滋病毒感染。