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02700 VAGINAL COATING BY MICROBICIDE FORMULATIONS: DIRECT MEASUREMENT IN WOMEN AND BIOPHYSICAL PREDICTION Katz, David F.* ** Rational microbicide design must objectively link formulation properties to biological functionality, which depends, in part, on extent and durability of epithelial coating. We measured quantitative details of vaginal gel coating in women (custom fiber optic device), in relation to predictions of biophysical theory and experiment. Five gels with different chemical structures and biophysical properties: KY Jelly and Conceptrol (cellulose); Replens and Advantage (polyacrylic acid); and Carraguard (carrageenan) underwent paired human in vivo studies plus in vitro measurements of salient properties, flow and surface adhesion. Mathematical models of flow and adhesion were also applied. We found significant differences in measures of in vivo vaginal distribution and retention by the gels (e.g. extent, uniformity, bare spots). These related to formulation properties as interpreted using principles of biophysics. For example, initial coating by Conceptrol was less complete and uniform, and more prone to bare spots, than that by Advantage. This was predicted, in part, by differences in viscosity and surface properties (whole, and diluted with simulants of vaginal fluid and semen), as explained by gel coating models. KY and Replens have distinct biophysical properties, and these are altered differently by interactions with ambient vaginal fluids suggesting different in vivo distributions. Initial in vivo analyses confirmed this. Formulation properties interact with details of formulation application (volume, location) as well as posture and movement, in governing coating distributions. (Supported by NIH AI48103, NIH HD41752 & FDA A60872). Professor David F. Katz |
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