Goethe Center for Scientific Computing, Kettenhofweg 139, Goethe University, 60325 Frankfurt a.M., Germany.
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260-4200, USA.
Eur J Pharm Biopharm. 2023 Jul;188:271-286. doi: 10.1016/j.ejpb.2023.01.025. Epub 2023 Feb 9.
This paper presents a computational model of molecular diffusion through the interfollicular stratum corneum. Specifically, it extends an earlier two-dimensional microscopic model for the permeability in two ways: (1) a microporous leakage pathway through the intercellular lipid lamellae allows slow permeation of highly hydrophilic permeants through the tissue; and (2) the model yields explicit predictions of both lateral (D‾) and transdermal (D‾) effective (average, homogenized) diffusivities of solutes within the tissue. We present here the mathematical framework for the analysis and a comparison of the predictions with experimental data on desorption of both hydrophilic and lipophilic solutes from human stratum corneum in vitro. Diffusion in the lipid lamellae is found to make the effective diffusivity highly anisotropic, with the predicted ratio D‾/D‾ ranging from 34 to 39 for fully hydrated skin and 150 to more than 1000 for partially hydrated skin. The diffusivities and their ratio are in accord with both experimental data and the results of mathematical analyses performed by others.
本文提出了一种通过毛囊间角质层进行分子扩散的计算模型。具体来说，它通过两种方式扩展了早期的二维微观模型的渗透性：（1）通过细胞间脂质层的微孔泄漏途径允许高度亲水的渗透物通过组织进行缓慢渗透；（2）该模型明确预测了组织内溶质的横向（D‾）和透皮（D‾）有效（平均、均匀化）扩散系数。本文介绍了分析的数学框架，并将预测结果与体外人体角质层对亲水性和疏水性溶质解吸的实验数据进行了比较。发现脂质层中的扩散使有效扩散系数具有高度各向异性，对于完全水合的皮肤，预测的 D‾/D‾比值范围为 34 到 39，对于部分水合的皮肤，比值范围为 150 到 1000 以上。扩散系数及其比值与实验数据以及其他人进行的数学分析结果一致。
