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

基本信息

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
项目类别：
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

项目摘要

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) 将安全、有效且易于逆转的避孕方案与针对性 HIV-1 传播的外用杀菌剂相结合，成为全球卫生优先事项。然而，目前尚无临床批准的女性控制双重保护技术来预防 HIV-1 性传播和意外怀孕。开发针对艾滋病毒和意外怀孕的有效 DPT 的一个瓶颈是将多种设计标准集成到单个设备中。我们假设，图案化的电纺纳米纤维浸有对艾滋病毒和精子具有特异性作用的试剂，旨在保护子宫颈和阴道，将为艾滋病毒性传播和怀孕的双重预防提供化学和物理屏障。我们建议通过使用可生物降解的纳米纤维进行阴道药物输送来改变现有 DPT 的发展范式，以实现以下具体目标：（1）静电纺丝纳米纤维用于不同化学类别药物（小分子药物和生物制剂）的伴随和持续释放； (2) 制备具有可控结构、机械强度和粘膜粘附性能的三维静电纺丝纳米纤维； (3)测量生殖器分泌物和侵蚀对纳米纤维避孕杀菌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； (5) 在小鼠模型中测量纳米纤维的生物分布和避孕活性。该提案的成功在于整合了生物材料合成和表征、艾滋病毒杀微生物剂开发和功效测试以及非激素避孕药开发和功效测试方面的研究。这种新型阴道药物递送平台有可能单独或组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，或设计用于直肠药物递送。公共卫生相关性：迫切需要女性控制的预防 HIV-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复合基质，以联合递送多种抑制 HIV-1 和精子的药物。这种方法将赋予妇女权力并为其提供多用途技术，以有效控制其生殖健康。