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: 10264922
• 负责人: JEFFREY T. JENSEN
• 金额: $ 75.45万
• 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/10264922
• 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; treatment as prevention; 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/艾滋病大流行和意外怀孕的双重影响构成了重大健康负担 妇女在全球范围内，证明了高效下一代多功能预防的发展 将安全，有效且易于可逆的长效避孕与艾滋病毒结合的技术（NGM） 预防。在这里，我们建议调整记忆电线铜内设备（IUD）框架作为一个平台 宫内递送抗逆转录病毒（AVR）药物可提供用户友好的HIV暴露前预防（PREP） 和避孕。我们建议评估与宫内节育器交付兼容的ARV药物输送系统的决斗 保护长达三年。在AIM 1中，我们将在AIM 1中制定候选抗病毒药物/前药固体分散体 矩阵，水库和电纺药物输送系统，并将其集成到现有的铜宫内 优化药物载荷，溶解速率，化学和功能稳定性以及与和稳定的整合 宫内节育器的功能属性。然后，我们将评估宫内的安全性和药代动力学作用 在狒狒中提供候选设备，并测量阴道，子宫颈和 子宫内膜。最后，在AIM 3中，我们将使用猕猴模型来评估药物的保护功效 针对重复的低剂量阴道SHIV162P3的HIV预防前预防的HIV递送系统 挑战。