A low-profile copper intrauterine device that delivers long-acting contraception an

摘要 艾滋病毒/艾滋病大流行和意外怀孕的双重影响是#年的主要健康负担。 并证明开发高效的下一代多用途预防措施是合理的 将安全、有效和易于逆转的长效避孕与艾滋病毒相结合的技术(NGM) 预防。在这里，我们建议采用记忆丝铜宫内节育器(IUD)框架作为平台 宫内交付抗逆转录病毒(AVR)药物以提供用户友好的艾滋病毒暴露前预防(PrEP) 和避孕措施。我们建议评估ARV给药系统与IUD给药系统在对决中的兼容性。 保护期限最高可达三年。在目标1中，我们将在以下方面制备候选抗病毒药物/前药物固体分散体 基质、储器和电纺药物输送系统，并将这些系统集成到现有的铜质IUD中，以 优化载药量、溶出度、化学稳定性和功能稳定性，并与药物稳定结合 宫内节育器的功能属性。然后我们将评估宫内注射的安全性和药代动力学效应。 在狒狒体内传递候选装置，并测量阴道、宫颈和子宫中的药物浓度 子宫内膜。最后，在目标3中，我们将使用猕猴模型来评估药物的保护效果-- 用于HIV暴露前预防重复小剂量阴道注射SHIV162P3的洗脱递送系统 挑战。

ABSTRACT The dual impacts of the HIV/AIDS pandemic and unintended pregnancies constitute a major health burden for women worldwide and justify the development of highly-effective next-generation multipurpose prevention technologies (NGM) that combine safe, effective, and easily reversible long-acting contraception with HIV prevention. Here, we propose to adapt a memory wire copper intrauterine device (IUD) frame as a platform for intrauterine delivery of antiretroviral (AVR) drugs to provide user friendly HIV pre-exposure prophylaxis (PrEP) and contraception. We propose to evaluate ARV drug delivery systems compatible with IUD delivery for duel- protection up to three years. In Aim 1, we will formulate candidate antiviral drug/prodrug solid dispersions in matrix, reservoir and electrospun drug delivery systems and integrate these into an existing copper IUD to optimize drug loading, dissolution rate, chemical and functional stability, and stable integration with and functional attributes of the IUD. We will then evaluate the safety and pharmacokinetic effects of intrauterine delivery of candidate devices in baboons, and measure drug concentrations in the vagina, cervix, and endometrium. Finally, in Aim 3 we will use the macaque model to evaluate the protective efficacy of the drug- eluting delivery system for HIV pre-exposure prophylaxis against a repeated low-dose vaginal SHIV162P3 challenge.