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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Savarese, Barbara M
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Duke University
Biomedical Engineering
Schools of Engineering
United States
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Lai, Bonnie E; Henderson, Marcus H; Peters, Jennifer J et al. (2009) Transport theory for HIV diffusion through in vivo distributions of topical microbicide gels. Biophys J 97:2379-87
Lai, Bonnie E; Xie, Yao Quan; Lavine, Michael L et al. (2008) Dilution of microbicide gels with vaginal fluid and semen simulants: effect on rheological properties and coating flow. J Pharm Sci 97:1030-8
Geonnotti, Anthony R; Furlow, Matthew J; Wu, Tianshi et al. (2008) Measuring macrodiffusion coefficients in microbicide hydrogels via postphotoactivation scanning. Biomacromolecules 9:748-51
Henderson, Marcus H; Couchman, Grace M; Walmer, David K et al. (2007) Optical imaging and analysis of human vaginal coating by drug delivery gels. Contraception 75:142-51
Kieweg, Sarah L; Katz, David F (2007) Interpreting properties of microbicide drug delivery gels: analyzing deployment kinetics due to squeezing. J Pharm Sci 96:835-50
Gupta, Kavita M; Barnes, Scott R; Tangaro, Rachel A et al. (2007) Temperature and pH sensitive hydrogels: an approach towards smart semen-triggered vaginal microbicidal vehicles. J Pharm Sci 96:670-81
Kieweg, Sarah L; Katz, David F (2006) Squeezing flows of vaginal gel formulations relevant to microbicide drug delivery. J Biomech Eng 128:540-53
Geonnotti, Anthony R; Katz, David F (2006) Dynamics of HIV neutralization by a microbicide formulation layer: biophysical fundamentals and transport theory. Biophys J 91:2121-30
Braun, Kelly E; Boyer, Jeffrey D; Henderson, Marcus H et al. (2006) Label-free measurement of microbicidal gel thickness using low-coherence interferometry. J Biomed Opt 11:020504
Owen, Derek H; Katz, David F (2005) A review of the physical and chemical properties of human semen and the formulation of a semen simulant. J Androl 26:459-69

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