Sustained release acyclovir for prophylaxis of genital herpes

描述（由申请人提供）：该项目的长期目标是通过开发基于缓释药物传递的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。5000万美国人感染了生殖器疱疹，这种疾病在世界上艾滋病毒高发地区很常见。由于生殖器疱疹极大地增加了艾滋病毒项目的传播性，因此开发一种有效的方法来减少HSV的传播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相关性。我们已经开发了一种平台技术，通过植入来持续释放广泛的药物，长期保持抗病毒水平。这项技术导致了更昔洛韦眼内植入物：Vitrasert(R)，被批准用于治疗艾滋病相关的巨细胞病毒性视网膜炎。我们建议利用这个平台来开发阿昔洛韦的阴道环缓释制剂。我们已经制定了原型环，在30天内以线性方式释放阿昔洛韦。在本一期项目中，我们拟在体外制备和测试阿昔洛韦缓释植入物，并在已建立的动物模型中测试其安全性和有效性。公共卫生相关性：生殖器疱疹感染大大增加了艾滋病毒传播的风险。这个项目的广泛长期目标是，通过开发一种有效的阴道内环形杀微生物剂，以阿昔洛韦的缓释药物输送为基础，保护目前未感染生殖器疱疹的妇女免受感染。我们将制定用于动物的阴道内装置原型，确认阿昔洛韦的安全性和长期给药，并在动物模型中验证局部使用阿昔洛韦可以预防感染的假设。成功地将无环鸟苷掺入环状杀微生物剂中，可能对艾滋病大流行病的演变产生巨大影响。

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.