Sustained release acyclovir for prophylaxis of genital herpes

缓释阿昔洛韦预防生殖器疱疹

• 批准号: 7619774
• 负责人: Thomas J. Smith
• 金额: $ 22.4万
• 依托单位: AURITEC PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7619774
• 关键词: Acquired Immunodeficiency Syndrome; Acyclovir; American; Animal Model; Animals; Antiviral Agents; Area; Clinical; Cytomegalovirus Retinitis; Data; Development; Devices; Dimensions; Disease; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Economic Development; Evolution; FDA approved; Foundations; Funding; Ganciclovir; Genital system; Goals; HIV; HIV Infections; Human; Implant; In Vitro; Infection; Infection prevention; Investigational Drugs; Knowledge; Lead; Living Standards; Marketing; Measurement; Methods; Modeling; Mus; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Prevalence; Process; Program Development; Prophylactic treatment; Recording of previous events; Reporting; Risk; Safety; Science; Services; Simplexvirus; System; Technology; Tenofovir; Testing; Therapeutic Agents; Tissues; Toxic effect; United States National Institutes of Health; Vaginal Ring; Water; Woman; Work; World Health Organization; base; empowered; genital herpes; high risk; implantation; innovation; microbicide; mouse model; novel; novel therapeutics; pandemic disease; prevent; programs; prophylactic; prototype; public health relevance; safety testing; transmission process

DESCRIPTION (provided by applicant): The broad long term goal of this project is to empower women to protect themselves from HSV and HIV infection through the development of an HSV microbicide based on sustained release drug delivery. Each day 15,000 people are infected with HIV- a growing majority of them women. Fifty million Americans are infected with genital herpes, and the disease is common in areas of the world of high HIV prevalence. Because genital herpes dramatically increases the transmissibility of HIV programs, the development of an effective method to reduce the spread of HSV is of high programmatic relevance to the NIH as well as other world health organizations. We have developed a platform technology for the sustained release of a broad range of drugs by implantation which maintains antiviral levels for long periods. This technology lead to the ganciclovir intraocular implant: the Vitrasert(R), approved for the treatment of AIDS related CMV retinitis. We propose to utilize this platform to develop sustained release vaginal ring formulations for acyclovir. We have formulated prototype rings that release acyclovir in a linear fashion over 30 days. In this Phase 1 project we propose to formulate and test sustained release acyclovir implants in vitro and then test their safety and efficacy in an established animal model. PUBLIC HEALTH RELEVANCE: Infection with genital herpes dramatically increases the risk of the spread of HIV. The broad long term goal of this project is to protect women currently uninfected by genital herpes from infection by developing an effective intravaginal ring microbicide based on the sustained release drug delivery of acyclovir. We will formulate prototype intravaginal devices for use in animals, confirm the safety and delivery of acyclovir over prolonged periods, and test the hypothesis that topical acyclovir can prevent infection in an animal model. The successful incorporation of acyclovir into a ring based microbicide could have a dramatic impact on the evolution of the AIDS pandemic.

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HSV杀微生物剂，使妇女能够保护自己免受HSV和HIV感染。每天有15 000人感染艾滋病毒，其中越来越多的是妇女。生殖器疱疹是一种常见的传染性疾病，它的发病率很高。由于生殖器疱疹大大增加了艾滋病毒项目的可传播性，因此开发一种有效的方法来减少HSV的传播对NIH以及其他世界卫生组织具有高度的项目相关性。我们开发了一种平台技术，通过植入持续释放多种药物，长期保持抗病毒水平。这项技术导致更昔洛韦眼内植入物：Vitrasert（R），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，开发缓释阴道环制剂阿昔洛韦。我们已经制定了原型环，释放阿昔洛韦在线性的方式超过30天。在这个第一阶段的项目中，我们建议制定和测试缓释阿昔洛韦植入剂在体外，然后测试其安全性和有效性在一个既定的动物模型。生殖器疱疹是一种传染性很强的疾病，它的传播途径有很多种。该项目广泛的长期目标是通过开发一种基于阿昔洛韦缓释药物递送的有效阴道内环杀微生物剂，保护目前未感染生殖器疱疹的妇女免受感染。我们将制定原型阴道内装置用于动物，确认安全性和长期提供的阿昔洛韦，并测试的假设，局部阿昔洛韦可以防止感染的动物模型。成功地将阿昔洛韦掺入环基杀微生物剂中可能对艾滋病流行的演变产生巨大影响。