Department of Chemical Engineering, The University of Illinois at Chicago, Chicago, Illinois 60607.
James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, Ohio 45267-0514.
J Pharm Sci. 2019 May;108(5):1692-1712. doi: 10.1016/j.xphs.2018.11.014. Epub 2018 Nov 17.
Owing to the systematic alignment and ordering of fatty acid and ceramide chains, lipid layers in biological membranes have strongly anisotropic diffusion properties. The diffusivity D for solute transport in the direction parallel to the lipid layer is typically 10-10 times the diffusivity D for the perpendicular direction. This article explores the consequences of this strong degree of anisotropy on solute diffusion through the stratum corneum (barrier) layer of the skin based on a realistic representation of a unit cell of the microstructure. Complementary numerical methods (smoothed particle hydrodynamics, finite differences) are used to solve the steady-state unit-cell diffusion problem leading to the average (homogenized, coarse-grained) diffusion tensor characterizing the tissue as an effective continuum. A parametric study is presented characterizing solute concentration profiles in detail for testosterone- and caffeine-like permeants, and it is shown that the results cannot be mimicked by calculations based on an isotropic lipid-phase diffusivity. The ratio of lateral to transdermal effective diffusivities calculated by the present model is of the order of 40 and 300 for fully hydrated (in vitro) and partially hydrated (in vivo) states, respectively. These values compare favorably with the results of recent experiments.
由于脂肪酸和神经酰胺链的系统排列和有序化，生物膜中的脂质层具有强烈各向异性的扩散特性。溶质在平行于脂质层方向上的扩散系数 D 通常是垂直方向上扩散系数 D 的 10-10 倍。本文基于皮肤角质层（屏障）层微观结构的单元的真实表示，探讨了这种强烈各向异性对溶质扩散的影响。补充的数值方法（平滑粒子流体动力学、有限差分）用于求解稳态单元扩散问题，从而得到表征组织为有效连续体的平均（均匀化、粗粒化）扩散张量。进行了参数研究，详细描述了睾酮和咖啡因类渗透物的溶质浓度分布，结果表明，基于各向同性脂质相扩散系数的计算无法模拟这些结果。本模型计算的侧向和透皮有效扩散系数之比在完全水合（体外）和部分水合（体内）状态下分别约为 40 和 300。这些值与最近实验的结果相当。
