A NanoGuard Vaginal Matrix as a Dual-Protection Contraceptive Microbicide

NanoGuard 阴道基质作为双重保护避孕杀菌剂

• 批准号: 8264681
• 负责人: Kim A. Woodrow
• 金额: $ 21.23万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8264681
• 关键词: AIDS/HIV problem; Anti-HIV Agents; Architecture; Barrier Contraception; Biocompatible Materials; Biodistribution; Biological Availability; Biomechanics; Breeding; Cervical; Cervix Uteri; Chemical Agents; Chemicals; Coitus; Contraceptive Agents; Contraceptive methods; Development; Devices; Drug Delivery Systems; Drug Design; Entire transverse folds of palate; Epithelium; Exhibits; Female; Film; HIV; HIV-1; Health; Health Priorities; Hormonal; In Vitro; Infection; Kinetics; Label; Local Microbicides; Measures; Mechanical Stress; Mechanics; Methods; Metric; Mucous Membrane; Mus; Pattern; Permeability; Pharmaceutical Preparations; Pregnancy; Prevention; Property; Reproductive Health; Reproductive Tract Infections; Research; Risk; Seminal fluid; Sperm Penetration; Structure; System; Technology; Testing; Tissue Model; Tissues; Tubular formation; Vagina; Woman; base; cellular targeting; contraceptive microbicide; design; efficacy testing; empowered; flexibility; genital secretion; global health; improved; microbicide; mouse model; nanofiber; nanoparticle; novel; pandemic disease; prevent; rectal; scaffold; small molecule; sperm cell; sperm function; success; transmission process; unintended pregnancy

DESCRIPTION (provided by applicant): The dual impacts of the HIV/AIDS pandemic and unintended pregnancies constitute a major health burden for women worldwide. As a consequence, dual protection technologies (DPT) combining safe, effective, and easily reversible options for contraception with a topical microbicide against sexual HIV-1 transmission are a global health priority. However, there is currently no clinically approved female-controlled dual protection technology to prevent sexual HIV-1 transmission and unintended pregnancies. A bottleneck for developing effective DPTs against HIV and unintended pregnancies is in the integration of multiple design criteria into a single device. We hypothesize that patterned electrospun nanofibers impregnated with agents that have specific action against HIV and sperm, and are designed to protect both the cervix and vagina, will provide a chemical and physical barrier for dual-prevention of sexual HIV transmission and pregnancy. We propose a paradigm shift from the development of existing DPTs by using biodegradable nanofibers for vaginal drug delivery that achieve the following specific aims: (1) Electrospin nanofibers for concomitant and sustained release of different chemical classes of agents (small molecule drug and biologics); (2) Fabricate three-dimensional electrospun nanofibers with controlled architecture, mechanical strength, and mucoadhesive properties; (3) measure effect of genital secretions and erosion on the release kinetics and activity of the nanofiber contraceptive microbicide; (4) measure biodistribution and anti-HIV activity of nanofibers in tissue explants; and (5) measure biodistribution and contraceptive activity of nanofibers in a mouse model. The success of this proposal is through integrating research on biomaterials synthesis and characterization, HIV microbicide development and efficacy testing, and non-hormonal contraceptive development and efficacy testing. This novel vaginal drug delivery platform could potentially be used for prevention of other sexually-transmitted or reproductive tract infections alone and in combination, intravaginal delivery of nanoparticles, or be designed for rectal drug delivery. PUBLIC HEALTH RELEVANCE: Female-controlled prevention methods against sexual HIV-1 transmission and pregnancy are critically needed. We propose a topical strategy that employs drug-eluting nanofibers that are assembled into a composite matrix to deliver in combination multiple drugs that inhibit HIV-1 and sperm. This approach will empower and provide women with a multipurpose technology for effective control of their reproductive health.

描述（由申请人提供）：艾滋病毒/艾滋病大流行和意外怀孕的双重影响构成了全世界妇女的主要健康负担。因此，双重保护技术（DPT）结合安全，有效和易于逆转的避孕选择与局部杀微生物剂防止性传播HIV-1是全球卫生的优先事项。然而，目前还没有临床批准的女性控制的双重保护技术来预防性传播艾滋病毒-1和意外怀孕。开发针对HIV和意外怀孕的有效DPT的瓶颈在于将多个设计标准整合到单个设备中。我们假设，图案化的静电纺丝纳米纤维浸渍有对艾滋病毒和精子具有特异性作用的试剂，并且旨在保护子宫颈和阴道，将为双重预防性艾滋病毒传播和怀孕提供化学和物理屏障。我们提出了一个范式的转变，从现有的DPT的发展，通过使用可生物降解的纳米纤维阴道给药，实现以下具体目标：（1）静电纺丝纳米纤维的伴随和持续释放的不同化学类别的药物（2）制造具有受控结构、机械强度和粘膜粘附性质的三维电纺纳米纤维;（3）测量生殖器分泌物和侵蚀对可吸收避孕杀微生物剂的释放动力学和活性的影响;（4）测量组织外植体中纳米纤维的生物分布和抗HIV活性;和（5）测量小鼠模型中纳米纤维的生物分布和避孕活性。这一建议的成功是通过整合生物材料合成和特性研究、艾滋病毒杀微生物剂的开发和功效测试以及非激素避孕药的开发和功效测试。这种新型的阴道给药平台可能单独或联合用于预防其他性传播或生殖道感染，阴道内递送纳米颗粒，或设计用于直肠给药。 公共卫生相关性：迫切需要由女性控制的预防艾滋病毒1性传播和怀孕的方法。我们提出了一种局部策略，采用药物洗脱纳米纤维组装成一个复合基质，提供多种药物，抑制HIV-1和精子的组合。这一办法将赋予妇女权力，并为她们提供有效控制其生殖健康的多用途技术。