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: 8499242
• 负责人: Kim A. Woodrow
• 金额: $ 18.34万
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8499242
• 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.

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球妇女的重大健康负担。结果，双重保护技术（DPT）结合了安全，有效且易于可逆的避孕方法和针对性HIV-1传播的局部杀菌剂的选择，这是全球健康的优先事项。但是，目前尚无临床批准的女性控制的双重保护技术，可以防止性HIV-1传播和意外怀孕。一种用于开发针对HIV和意外怀孕的有效DPT的瓶颈是将多个设计标准整合到单个设备中。我们假设具有对艾滋病毒和精子具有特定作用的药物浸渍的图案性电纺纳米纤维，并旨在保护子宫颈和阴道，将为性和物理屏障提供双重预防性HIV传播和妊娠的化学障碍。我们提出，通过使用可生物降解的纳米纤维进行阴道药物递送，从现有DPT的发展进行范式转变，以实现以下特定目的：（1）静电素纳米纤维，用于伴随和持续释放不同化学类药物的药物（小分子药物和生物学）； （2）制造具有控制结构，机械强度和粘膜性能的三维电纺纳米纤维； （3）生殖器分泌物和侵蚀对纳米纤维避孕菌物释放动力学和活性的测量影响； （4）测量组织外植体中纳米纤维的生物分布和抗HIV活性； （5）测量小鼠模型中纳米纤维的生物分布和避孕活性。该提案的成功是通过整合有关生物材料合成和表征，HIV杀菌剂的发育和疗效测试以及非激素避孕药的发展和效能测试的研究。这个新型的阴道药物输送平台可能仅用于预防其他性传播或生殖道感染，并结合使用，纳米颗粒的阴道内输送，或设计用于直肠药物的递送。