Intravaginal ring microbicide formulations comprising multiple anti-HIV agents

描述（由申请人提供）：该项目的广泛长期目标是通过基于我们临床证明的缓释技术平台开发改进的杀微生物剂，使妇女能够保护自己免受艾滋病毒感染。使用该平台，用于广泛药物的药物递送装置已获得FDA批准，并已在临床上使用。更昔洛韦眼内植入物：Vitrasert（r），被批准用于治疗艾滋病相关的CMV视网膜炎，将相对可溶的抗病毒药物更昔洛韦释放到眼睛中，持续8个月。Retisert（r）释放相对不溶性的类固醇氟轻松丙酮长达三年。我们建议利用这个平台开发抗逆转录病毒药物替诺福韦和TMC 120的持续释放阴道环杀微生物剂制剂。在该项目的前两年（R21），我们将评估这样的假设，即当掺入环制剂中时，前体药物富马酸替诺福韦酯作为候选杀微生物剂优于母体药物替诺福韦酯上级。在项目的第二阶段（R33），我们将生产和测试含有多种抗病毒剂的环制剂。我们假设，使用我们独特的药物递送平台，将多种药物并入我们的系统中不会损失洗脱特征。该项目的成功完成将导致提交研究性新药豁免（IND），从而导致这些制剂的临床试验。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，通过开发基于抗病毒剂缓释药物输送的改进的杀微生物剂阴道环制剂，增强妇女保护自己免受艾滋病毒感染的能力。我们经过临床验证的缓释药物递送平台独特地允许我们递送高和低水溶性的药物。我们建议利用该平台技术开发潜在杀微生物剂替诺福韦和TMC-120的长期阴道环制剂。

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 our clinically proven sustained release technology platform. Using this platform drug delivery devices for a broad range of drugs have been approved by the FDA and are in current clinical use. The ganciclovir intraocular implant: the Vitrasert(r), approved for the treatment of AIDS related CMV retinitis releases the relatively soluble antiviral ganciclovir into the eye for a period of eight months. The Retisert(r) releases the relatively insoluble steroid fluocinolone acetonide for up to three years. We propose to utilize this platform to develop sustained release vaginal ring microbicide formulations for the antiretroviral agents tenofovir and TMC 120. In the first two years of this project (R21) we will evaluate the hypothesis that, when incorporated into a ring formulation, the prodrug tenofovir disoproxil fumarate is superior to the parent drug tenofovir as candidate microbicide. In the second phase of the project (R33) we will manufacture and test ring formulations containing multiple antiviral agents. We hypothesize that, using our unique drug delivery platform, there will be no loss of elution characteristics with the incorporation of multiple drugs into our system. The successful completion of this project will result in the submission of an investigational new drug exemption (IND) leading to clinical trials for these formulations. 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 improved vaginal ring formulations for microbicides based on the sustained release drug delivery of antiviral agents. Our clinically proven sustained release drug delivery platform uniquely allows us to deliver drug of both high and low aqueous solubility. We propose to utilize this platform technology to develop long-term vaginal ring formulations for the potential microbicides tenofovir and TMC-120.