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 STI 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 the applicant?s laboratory, will be employed to quantitate carrageenan formulation coating thickness distributions in women. A series of studies will contrast important biological and biophysical factors, e.g., time and motion after formulation application, cycle phase and simulated coitus. The results will contribute immediately to evaluation of the novel carrageenan formulations, and determinations of which one(s) have the greatest potential as microbicides for women. 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. The apliocant's 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 the applicant 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 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, and to create and apply a biophysical test bed for evaluation and optimization of the novel carrageenan formulations. This will provide an objective and accurate means of relating formulation properties directly to microbicidal function. It will be an unprecedented, but necessary component of the overall biological and biophysical evaluation of the novel carrageenan formulations.
