A NanoGuard Vaginal Matrix as a Dual-Protection Contraceptive Microbicide

说明（由申请人提供）：艾滋病毒/艾滋病流行病和意外怀孕的双重影响对全世界妇女构成了重大的健康负担。因此，双重保护技术（DPT）将安全、有效和易于逆转的避孕选择与局部杀微生物剂相结合，以防止HIV-1性传播，是全球卫生的重点。然而，目前还没有临床批准的女性控制的双重保护技术来防止HIV-1性传播和意外怀孕。开发有效预防艾滋病毒和意外怀孕的dpt的瓶颈是将多种设计标准整合到一个设备中。我们假设，静电纺丝纳米纤维浸渍了对HIV和精子有特定作用的试剂，并设计用于保护子宫颈和阴道，将提供化学和物理屏障，双重预防HIV的性传播和怀孕。我们建议从现有dpt的发展模式转变，使用可生物降解的纳米纤维进行阴道给药，实现以下具体目标：(1)电自旋纳米纤维用于伴随和持续释放不同化学类别的药物（小分子药物和生物制剂）；(2)制备具有可控结构、机械强度和粘接性能的三维静电纺纳米纤维；(3)测定生殖道分泌物和侵蚀对纳米纤维避孕杀微生物剂释放动力学和活性的影响；(4)测定纳米纤维在组织外植体中的生物分布和抗hiv活性；(5)测定纳米纤维在小鼠模型中的生物分布和避孕活性。该提案的成功是通过整合生物材料的合成和表征，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的研究。这种新型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，阴道内给药纳米粒子，或设计用于直肠给药。

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.