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

摘要 艾滋病毒/艾滋病大流行病和意外怀孕的双重影响对妇女构成重大健康负担， 并证明开发高效的下一代多用途预防是合理的 将联合收割机安全、有效、易逆转的长效避孕与艾滋病毒结合起来的技术 预防在这里，我们建议采用记忆线铜宫内节育器（IUD）框架作为平台， 宫内注射抗逆转录病毒（AVR）药物，以提供用户友好的艾滋病毒暴露前预防（PrEP） 和避孕。我们建议评估ARV药物输送系统与宫内节育器输送兼容， 保护期长达三年。在目标1中，我们将配制候选抗病毒药物/前药固体分散体， 基质、储库和静电纺丝药物递送系统，并将这些整合到现有的铜IUD中， 优化载药量、溶出速率、化学和功能稳定性，并与 IUD的功能属性。然后我们将评估子宫内给药的安全性和药代动力学效应。 在狒狒中递送候选装置，并测量阴道、子宫颈和 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功效- 用于HIV暴露前预防的洗脱给药系统，用于反复低剂量阴道SHIV 162 P3 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.