Intravaginal ring microbicide formulations comprising multiple anti-HIV agents

描述（由申请人提供）：这个项目的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。使用该平台的药物输送装置用于广泛的药物已被FDA批准，目前正在临床使用。更昔洛韦眼内植入物：批准用于治疗艾滋病相关巨细胞病毒性视网膜炎的Vitrasert(r)将相对可溶性的抗病毒药物更昔洛韦释放到眼睛中，为期8个月。瑞沙特(r)释放相对不溶性类固醇氟西诺酮醋酸酯长达三年。我们建议利用这一平台开发抗逆转录病毒药物替诺福韦和tmc120的缓释阴道环杀微生物制剂。在这个项目的前两年（R21），我们将评估假设，当纳入环制剂时，前药富马酸替诺福韦二氧吡酯优于母药替诺福韦作为候选杀微生物剂。在该项目的第二阶段（R33），我们将生产和测试含有多种抗病毒药物的环状制剂。我们假设，使用我们独特的药物输送平台，将多种药物合并到我们的系统中不会失去洗脱特性。该项目的成功完成将导致提交研究性新药豁免（IND），从而导致这些配方的临床试验。每天有15 000人感染艾滋病毒，大多数在撒哈拉以南非洲，妇女通过异性性行为感染的比例越来越高。这个项目的广泛长期目标是，通过开发基于抗病毒药物持续释放的杀微生物剂的改进阴道环配方，使妇女有能力保护自己免受艾滋病毒感染。我们经过临床验证的缓释药物输送平台独特地允许我们输送高和低水溶性药物。我们建议利用这一平台技术为潜在的杀菌剂替诺福韦和TMC-120开发长期阴道环制剂。

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.