Kim Y H, Ghanem A H, Higuchi W I
Department of Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City 84112.
Semin Dermatol. 1992 Jun;11(2):145-56.
An in vitro physical model approach for describing and predicting transport of molecules and ions across skin is examined. The proposed model is represented by two transport-resistant layers in series: the stratum corneum and the epidermis plus dermis. The stratum corneum is regarded as the principal barrier to transport and is composed of two parallel pathways: the lipoidal pathway and the pore pathway. The epidermis-dermis is treated as a porous membrane. The model predicts three regimes for the transport behavior of permeants, and these predictions have been compared with experimental permeability coefficient data obtained with hairless mouse skin in a two-chamber (aqueous) diffusion cell. The model predicts (1) that extremely lipophilic molecules are rate-limited by the epidermis-dermis and have a limiting permeability coefficient value; (2) that extremely polar permeants are rate-limited by the pore pathway of the stratum corneum with its limiting permeability coefficient; and (3) that permeants with intermediate polarity are transported via the lipoidal pathway and exhibit a lipophilicity-dependent permeability coefficient. Experimental data involving a large number of permeants are found to be consistent with these model predictions. The model approach also has been applied in the study of the mechanism(s) of skin transport enhancement induced by short-chain alkanols in aqueous media. A possible mode of enhancing the lipoidal pathway at low concentrations of the alkanols may involve the polar head region of the lipid bilayer or the region slightly below the polar head plane, or both; alkanols may solvate the lipid-water interface, intercalating and disrupting the interactions of the upper regions of the alkyl chains and the interactions between the polar head groups. This could result in an increase in both diffusivity and partitioning tendency for a permeant in this microenvironment. At higher alkanol concentrations, the pore pathway becomes dominant in controlling the transport of the permeants across the stratum corneum.
研究了一种用于描述和预测分子与离子经皮转运的体外物理模型方法。所提出的模型由两个串联的转运阻力层表示：角质层以及表皮加真皮。角质层被视为转运的主要屏障，由两条平行途径组成：脂质途径和孔隙途径。表皮 - 真皮被视为多孔膜。该模型预测了渗透物转运行为的三种状态，并且这些预测已与在双室（水性）扩散池中用无毛小鼠皮肤获得的实验渗透系数数据进行了比较。该模型预测：（1）极亲脂性分子的转运速率受表皮 - 真皮限制，具有极限渗透系数值；（2）极极性渗透物的转运速率受角质层孔隙途径及其极限渗透系数限制；（3）中等极性的渗透物通过脂质途径转运，并表现出与亲脂性相关的渗透系数。发现涉及大量渗透物的实验数据与这些模型预测一致。该模型方法还已应用于研究水性介质中短链烷醇诱导的皮肤转运增强机制。在低浓度烷醇下增强脂质途径的一种可能方式可能涉及脂质双层的极性头部区域或极性头部平面稍下方的区域，或两者；烷醇可能使脂质 - 水界面溶剂化，插入并破坏烷基链上部区域的相互作用以及极性头部基团之间的相互作用。这可能导致渗透物在这种微环境中的扩散率和分配趋势增加。在较高的烷醇浓度下，孔隙途径在控制渗透物穿过角质层的转运中起主导作用。
