Drug delivery of topical microbicidal molecules against HIV offers promise as a modality to prevent sexual transmission of the virus. Success of any microbicide product depends, in an interactive way, upon its drug (the microbicide active pharmaceutical ingredient, API) and its delivery system (e.g. a gel, film or intravaginal ring). There is a widespread agreement that more effective drug delivery vehicles, as well as better APIs, must be developed to improve the efficacy of microbicide products. Non-Newtonian gels are primary microbicide vehicles, but those to date have been created with limited understanding of how their properties govern their spreading and retention in the vagina, which, in turn, govern successful drug delivery. Here, we apply fundamental fluid mechanical and physicochemical transport theory to help better understand how successful microbicide API delivery depends upon properties of a gel and the vaginal environment. We address several critical components of this complex process, including: elastohydrodynamic flow of the bolus of a non-Newtonian fluid; and mass transfer due to inhomogeneous dilution of the gel by vaginal fluid contacting it along a moving boundary (the locally deforming vaginal epithelial surface). Local dilution of gel alters local rheological properties. We evaluated this experimentally, delineating the way that constitutive parameters of a shear-thinning gel are modified by dilution. We supplement the Reynolds lubrication equation with a mass conservation equation to model diluting fluid movement across the moving vaginal epithelial surface and into the gel bolus. This is a physicochemically complex phenomenon that is not well understood. We implement a boundary flux model based upon the elevated hydrodynamic pressures in the cells. Results show that this model produces fluxes that lie within the range of mean values that have been reported. Further experimental characterization of the vaginal wall is required for a more precise set of parameters and a more sophisticated theoretical treatment of epithelium.

针对 HIV 的局部杀微生物分子的药物递送有望作为一种预防病毒性传播的方式。任何杀微生物剂产品的成功都以交互方式取决于其药物（杀微生物剂活性药物成分，API）及其递送系统（例如凝胶、薄膜或阴道环）。人们普遍认为，必须开发更有效的药物传递载体以及更好的 API，以提高杀微生物剂产品的功效。非牛顿凝胶是主要的杀微生物剂载体，但迄今为止，人们对其特性如何控制其在阴道中的扩散和滞留的了解有限，而这反过来又控制着药物的成功输送。这里，我们应用基本的流体机械和物理化学传输理论来帮助更好地了解杀微生物剂 API 的成功输送如何取决于凝胶的特性和阴道环境。我们解决了这个复杂过程的几个关键组成部分，包括： 非牛顿流体团块的弹性流体动力学流动；由于阴道液体沿移动边界（局部变形的阴道上皮表面）接触凝胶而导致凝胶的不均匀稀释引起的质量转移。凝胶的局部稀释会改变局部流变特性。我们通过实验对此进行了评估，描绘了通过稀释修改剪切稀化凝胶的组成参数的方式。我们用质量守恒方程补充雷诺润滑方程，以模拟穿过移动阴道上皮表面并进入凝胶团的稀释流体运动。这是一种尚未完全了解的物理化学复杂现象。我们基于细胞中升高的流体动压实施边界通量模型。结果表明，该模型产生的通量位于已报告的平均值范围内。需要对阴道壁进行进一步的实验表征，以获得更精确的参数集和更复杂的上皮理论治疗。结果表明，该模型产生的通量位于已报告的平均值范围内。需要对阴道壁进行进一步的实验表征，以获得更精确的参数集和更复杂的上皮理论治疗。结果表明，该模型产生的通量位于已报告的平均值范围内。需要对阴道壁进行进一步的实验表征，以获得更精确的参数集和更复杂的上皮理论治疗。