Biophysics of Microbicides for STD Prevention

描述(由申请者提供)：该项目的目标是开发和 应用一种新的方法来表征杀微生物剂的部署 女性的配方，并阐明了支配 调配--配方药在阴道内的涂抹和保留 上皮面。部署的确切性质足以满足 对性病病原体的预防措施尚不清楚，对 任何配方在妇女中的部署特点。因此，这个项目将 获取前所未有的知识和数据。一种新的阴道内光学传感技术 我们实验室开发的仪器将被用于定量配方 女性的涂层厚度分布，包括其与局部的稀释 体液和pH值。一系列研究将对比重要的生物学和 生物物理因素，例如施药后的时间和运动、周期 阶段和模拟性交-用于一套当代配方，用作 阴道润滑剂、避孕药和/或被认为是潜在的性传播疾病 预防材料。这一结果将直接与广泛的 杀微生物剂开发中的基础生物学和临床研究的范围。 该项目还将采用客观的生物物理分析、实验和 理论上，以发展配方性能和 部署特征。目前几乎没有这样的知识， 也没有方法论来获得它。我们的方法是开发一套集成在 显著生物流体机械过程的体外实验模拟 在阴道内产生配方流动和滞留。对于每个此类进程 我们还将发展流体力学理论，从生物学角度预测 重要终点(例如配方铺展率、层厚度和 性质)使用配方性质的测量值作为输入。 理论和实验之间的对应将提供一种物理手段 体外方法的验证。 该项目的最终目标将是将体外方法与体内 活体结果。这将是一项交叉验证分析，其中衡量 体内部署与体外预测有关，首先是从 模拟，然后从数学模型本身。在一定程度上 如果建立了后一种联系，我们将制定一个目标和 将配方性能直接与杀微生物剂关联的准确方法 功能。如果我们的体外方法学是准确的，它将 提供一种非常有用且经济实惠的方法来评估当前 以及设计新的和改进的配方。它还将提供 史无前例的与STD感染机制相关的生物物理数据 女人。

DESCRIPTION (Provided by Applicant): The goal of this project is to develop and apply a new methodology that characterizes deployment of microbicidal formulations in women, and that elucidates biophysical mechanisms which govern deployment - the spreading and retention of formulations over the intra-vaginal epithelial surfaces. The precise nature of deployment that is sufficient for prophylaxis against STD pathogens is unknown, and there is little knowledge of deployment characteristics of any formulation in women. This project will thus obtain unprecedented knowledge and data. A new intravaginal optical sensing device, developed by our laboratory, will be employed to quantitate formulation coating thickness distributions in women, including their dilution with local fluids and pH. A series of studies will contrast important biological and biophysical factors, e.g. time and motion after formulation application, cycle phase and simulated coitus - for a set of contemporary formulations, used as vaginal lubricants, contraceptives, and/or being considered as potential STD prophylactic materials. The results will have immediate relevance to a broad spectrum of basic biological and clinical studies in microbicide development. This project will also employ objective biophysical analysis, experimental and theoretical, to develop relationships between formulation properties and deployment characteristics. At present there is virtually no such knowledge, nor methodology to obtain it. Our approach is to develop a set of integrated in vitro experimental simulations of salient bio-fluid mechanical processes that produce formulation flow and retention within the vagina. For each such process we will also develop fluid mechanical theory that predicts biologically important endpoints (e.g. formulation spreading rates, layer thicknesses and properties) using measured values of formulation properties as inputs. Correspondence between theory and experiment will provide a means of physical validation of the in vitro methods. The final goal of the project will be to link the in vitro methods with the in vivo results. This will be a cross validation analysis, in which measures of deployment in vivo are related to predictions in vitro, first from the simulations and then from the mathematical models themselves. To the extent that the latter link is established, we will have developed an objective and accurate means of relating formulation properties directly to microbicidal function. To the extent that our in vitro methodology is accurate, it will provide an extremely useful and cost effective means of evaluating current formulations and designing new and improved ones. It will also provide unprecedented biophysical data relevant to mechanisms of STD infection in women.