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

一种低调的铜宫内节育器，可提供长效避孕和

• 批准号: 10158876
• 负责人: JEFFREY T. JENSEN
• 金额: $ 74.87万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10158876
• 关键词: AIDS prevention; AIDS/HIV problem; Address; Adherence; Alloys; Anatomy; Anti-Retroviral Agents; Antiviral Agents; Atopobium vaginae; Benchmarking; Biopsy; Blood Circulation; Cells; Cervical; Cervix Uteri; Chemicals; Clinical; Clinical Data; Contraceptive Agents; Contraceptive methods; Copper; Copper Intrauterine Devices; Cytology; Data; Development; Device Designs; Devices; Dose; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Drug resistance; Electrospinning; Endocervix; Endometrial; Endometrium; Ethylenes; Exocervix; FDA approved; Female; HIV; HIV-1; Health; Health Priorities; Hormones; Human; Injectable; Intrauterine Devices; Lead; Levonorgestrel; Macaca; Macaca mulatta; Measurement; Measures; Memory; Methods; Modeling; Monitor; Mucous Membrane; Operative Surgical Procedures; Oral; Papio; Permeability; Pharmaceutical Preparations; Pharmacologic Substance; Plasma; Polyurethanes; Positioning Attribute; Pregnancy; Prevention; Prevention strategy; Prodrugs; Proteins; Recording of previous events; Reporting; Reproductive Health; Safety; Serum; Shapes; Site; Solid; Solubility; Study models; Surgical sutures; System; Systemic infection; Technology; Tissues; Ultrasonography; Uterine cavity; Uterus; Vagina; Width; Woman; base; cervicovaginal; contraceptive efficacy; cytokine; drug efficacy; efficacy study; flexibility; global health; implantable device; innovation; microbicide; microbiota; next generation; novel; pandemic disease; polydimethylsiloxane; pre-exposure prophylaxis; prevent; protective efficacy; prototype; sexual HIV transmission; simian human immunodeficiency virus; success; transmission process; unintended pregnancy; user-friendly; vinyl acetate

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.

抽象的 艾滋病毒/艾滋病流行和意外怀孕的双重影响构成了重大的健康负担 全世界妇女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、有效且易于逆转的长效避孕药与艾滋病毒结合起来的技术 (NGM) 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 宫内递送抗逆转录病毒 (AVR) 药物，以提供用户友好的 HIV 暴露前预防 (PrEP) 和避孕。我们建议评估与宫内节育器递送兼容的抗逆转录病毒药物递送系统，以实现双重目的 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、储库和电纺药物输送系统，并将它们集成到现有的铜宫内节育器中 优化载药量、溶出率、化学和功能稳定性以及与 和 的稳定集成 IUD 的功能属性。然后我们将评估宫内节育器的安全性和药代动力学作用 将候选装置递送到狒狒体内，并测量阴道、子宫颈和阴道中的药物浓度 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功效—— 用于针对反复低剂量阴道 SHIV162P3 进行 HIV 暴露前预防的洗脱输送系统 挑战。