ANIMAL MODELS FOR COMBINATION MICROBICIDES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 外用杀微生物剂是预防艾滋病毒/性病传播的一个重要的潜在战略。希望局部杀微生物剂产品在单次和重复使用后有效预防HIV和STD感染，同时不刺激粘膜表面或不利地影响阴道或直肠的正常植物群。在推荐广泛的阴道内或直肠内使用之前，必须对开发的局部杀微生物产品的体内活性进行评估。 由于临床试验对于筛选目的来说过于繁琐和昂贵，因此需要使用动物模型。本研究的主要目的是开发一种组合外用杀微生物剂产品。也就是说，一种产品将由一种以上的活性（抗菌）化合物组成，提供一种以上的对抗艾滋病毒和其他性传播感染的作用模式。 随着拟议的组合局部杀微生物剂配方的发展，我们将使用我们建立的局部杀微生物剂安全性试验动物模型评估中间配方产品在直肠和阴道环境中的安全性。这些拟议的研究是弥合旨在预防艾滋病毒/性传播感染传播的实验室和临床研究之间差距的关键。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Topical microbicides represent an important potential strategy for preventing the transmission of HIV/STD. It is desirable that a topical microbicide product be effective in preventing HIV and STD infections while not irritating the mucosal surface or adversely affecting normal flora of the vagina or rectum, after single and repeated use. It is essential that the in vivo activity of developing topical microbicidal products be evaluated prior to recommendations for widespread intravaginal or rectal use. Because clinical trials are too cumbersome and expensive for screening purposes, animal models need to be used. The primary goal of this study is to develop a combination topical microbicide product. That is to say, a product which will be composed of more than one active (antimicrobial) compound, providing more than one mode of action against HIV and other STI. As the proposed combination topical microbicide formulation evolves, we will assess safety of intermediary formulated products in the rectal and vaginal environments using our established animal model for topical microbicide safety testing. These proposed studies are key to bridging the gap between laboratory and clinical studies aimed at preventing the spread of HIV/STI.