Tasoglu Savas, Rohan Lisa C, Katz David F, Szeri Andrew J
Department of Mechanical Engineering, University of California, Berkeley, California 94720-1740, USA.
Phys Fluids (1994). 2013 Mar;25(3):31901. doi: 10.1063/1.4793598. Epub 2013 Mar 4.
There is a widespread agreement that more effective drug delivery vehicles with more alternatives, as well as better active pharmaceutical ingredients (APIs), must be developed to improve the efficacy of microbicide products. For instance, in tropical regions, films are more appropriate than gels due to better stability of drugs at extremes of moisture and temperature. Here, we apply fundamental fluid mechanical and physicochemical transport theory to help better understand how successful microbicide API delivery depends upon properties of a film and the human reproductive tract environment. Several critical components of successful drug delivery are addressed. Among these are: elastohydrodynamic flow of a dissolved non-Newtonian film; mass transfer due to inhomogeneous dilution of the film by vaginal fluid contacting it along a moving boundary (the locally deforming vaginal epithelial surface); and drug absorption by the epithelium. Local rheological properties of the film are dependent on local volume fraction of the vaginal fluid. We evaluated this experimentally, delineating the way that constitutive parameters of a shear-thinning dissolved film are modified by dilution. To develop the mathematical model, we integrate the Reynolds lubrication equation with a mass conservation equation to model diluting fluid movement across the moving vaginal epithelial surface and into the film. This is a complex physicochemical phenomenon that is not well understood. We explore time- and space-varying boundary flux model based upon osmotic gradients. Results show that the model produces fluxes that are comparable to experimental data. Further experimental characterization of the vaginal wall is required for a more precise set of parameters and a more sophisticated theoretical treatment of epithelium.
人们普遍认为，必须开发出具有更多选择的更有效的药物递送载体以及更好的活性药物成分（API），以提高杀微生物剂产品的疗效。例如，在热带地区，由于药物在极端湿度和温度下具有更好的稳定性，薄膜比凝胶更合适。在此，我们应用基本的流体力学和物理化学传输理论，以帮助更好地理解成功的杀微生物剂API递送如何取决于薄膜的特性和人类生殖道环境。文中讨论了成功药物递送的几个关键组成部分。其中包括：溶解的非牛顿薄膜的弹性流体动力流动；沿移动边界（局部变形的阴道上皮表面）与阴道液接触导致薄膜不均匀稀释引起的传质；以及上皮细胞对药物的吸收。薄膜的局部流变特性取决于阴道液的局部体积分数。我们通过实验对此进行了评估，描绘了剪切稀化溶解薄膜的本构参数因稀释而改变的方式。为了建立数学模型，我们将雷诺润滑方程与质量守恒方程相结合，以模拟稀释流体在移动的阴道上皮表面并进入薄膜的运动。这是一种尚未得到充分理解的复杂物理化学现象。我们探索基于渗透梯度的时空变化边界通量模型。结果表明，该模型产生的通量与实验数据相当。为了获得更精确的参数集和对上皮细胞进行更复杂的理论处理，需要对阴道壁进行进一步的实验表征。
