Rim Jee E, Pinsky Peter M, van Osdol William W
Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
Ann Biomed Eng. 2009 Jun;37(6):1217-29. doi: 10.1007/s10439-009-9678-1. Epub 2009 Mar 25.
This study addresses the modeling of transdermal diffusion of drugs to better understand the permeation of molecules through the skin, especially the stratum corneum, which forms the main permeation barrier to percutaneous permeation. In order to ensure reproducibility and predictability of drug permeation through the skin and into the body, a quantitative understanding of the permeation barrier properties of the stratum corneum (SC) is crucial. We propose a multiscale framework of modeling the multicomponent transdermal diffusion of molecules. The problem is divided into subproblems of increasing length scale: microscopic, mesoscopic, and macroscopic. First, the microscopic diffusion coefficient in the lipid bilayers of the SC is found through molecular dynamics (MD) simulations. Then, a homogenization procedure is performed over a model unit cell of the heterogeneous SC, resulting in effective diffusion parameters. These effective parameters are the macroscopic diffusion coefficients for the homogeneous medium that is "equivalent" to the heterogeneous SC, and thus can be used in finite element simulations of the macroscopic diffusion process. The resulting drug flux through the skin shows very reasonable agreement to experimental data.
本研究致力于药物经皮扩散的建模，以更好地理解分子透过皮肤的渗透过程，尤其是穿过构成经皮渗透主要屏障的角质层。为确保药物透过皮肤并进入体内的过程具有可重复性和可预测性，定量了解角质层（SC）的渗透屏障特性至关重要。我们提出了一个用于模拟分子多组分经皮扩散的多尺度框架。该问题被划分为长度尺度不断增加的子问题：微观、介观和宏观。首先，通过分子动力学（MD）模拟确定SC脂质双层中的微观扩散系数。然后，对异质SC的模型单元进行均匀化处理，得到有效扩散参数。这些有效参数是与异质SC“等效”的均匀介质的宏观扩散系数，因此可用于宏观扩散过程的有限元模拟。通过皮肤产生的药物通量与实验数据显示出非常合理的一致性。
