Biophysics of Microbicides for STD Prevention

描述（由申请人提供）：本项目的目标是开发和 应用一种新的方法， 制剂，并阐明生物物理机制， 展开-制剂在阴道内的扩散和保留 上皮表面部署的确切性质足以 对性病病原体的预防是未知的，也有很少的知识， 任何制剂在女性中的部署特征。该项目将 获得前所未有的知识和数据。一种新的阴道内光学传感器 本实验室开发的装置将用于定量制剂 女性的涂层厚度分布，包括局部稀释 一系列的研究将对比重要的生物和 生物物理因素，例如制剂施用后的时间和运动，周期 阶段和模拟性交-对于一组当代制剂，用作 阴道润滑剂，避孕药，和/或被认为是潜在的STD 预防材料。结果将直接关系到广泛的 杀微生物剂开发的基础生物学和临床研究范围。 该项目还将采用客观的生物物理分析、实验和 理论上，开发配方特性和 部署特点。目前几乎没有这样的知识， 也没有方法来获得它。我们的方法是开发一套集成在 突出的生物流体机械过程的体外实验模拟， 产生阴道内的制剂流动和滞留。对于每个这样的过程， 我们还将发展流体力学理论， 重要的终点（例如制剂铺展速率、层厚度和 性质），使用制剂性质的测量值作为输入。 理论和实验之间的一致性将提供一种物理手段， 体外方法的验证。 该项目的最终目标是将体外方法与体内方法联系起来。 体内结果。这将是一个交叉验证分析，其中的措施 体内部署与体外预测有关，首先来自 模拟，然后从数学模型本身。尽 如果建立了后一种联系，我们将制定一个目标， 将配方特性与杀微生物剂直接关联的精确方法 功能在我们的体外方法学准确的程度上， 提供了一个非常有用和成本效益的手段，评估目前的 配方和设计新的和改进的。它还将提供 前所未有的生物物理数据有关的性病感染机制， 妇女

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.