Raykar P V, Fung M C, Anderson B D
Department of Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City 84112.
Pharm Res. 1988 Mar;5(3):140-50. doi: 10.1023/a:1015956705293.
The uptake of a series of hydrocortisone esters varying in lipophilicity from water into untreated and delipidized human stratum corneum has been determined. The partition coefficients of solutes into fully hydrated stratum corneum are postulated to represent the separate contributions of three structurally distinct domains--the extractable lipids, protein, and the solvent domain. The solvent domain was assumed to have the properties of bulk water. The relative affinities of the protein and lipid domains of stratum corneum for solutes varying in structure were determined by comparing solute uptake in untreated and delipidized stratum corneum. Partitioning into the extracted lipids was also examined. Solute uptake into stratum corneum may be governed by the protein domain, the lipid domain, or a combination of the two, depending on solute lipophilicity. Due to differences in the selectivity of the two domains, a change in uptake mechanism occurs with increasing solute lipophilicity from protein-dominated uptake for hydrophilic solutes to lipid domain-dominated uptake for lipophilic solutes. The stratum corneum lipid content, which varies dramatically from individual to individual (3-46% in this study), is an important determinant of the affinity of the stratum corneum for highly lipophilic solutes but has no effect on the uptake of hydrophilic solutes.
已测定了一系列亲脂性不同的氢化可的松酯从水进入未处理和脱脂的人体角质层的摄取情况。溶质在完全水合角质层中的分配系数被假定为代表三个结构不同区域（可提取脂质、蛋白质和溶剂区域）的单独贡献。溶剂区域被假定具有大量水的性质。通过比较溶质在未处理和脱脂角质层中的摄取情况，确定了角质层蛋白质和脂质区域对结构不同的溶质的相对亲和力。还研究了溶质在提取脂质中的分配情况。溶质进入角质层的摄取可能由蛋白质区域、脂质区域或两者共同控制，这取决于溶质的亲脂性。由于两个区域选择性的差异，随着溶质亲脂性的增加，摄取机制会发生变化，从亲水性溶质以蛋白质为主导的摄取转变为亲脂性溶质以脂质区域为主导的摄取。角质层脂质含量在个体之间差异很大（本研究中为3 - 46%），是角质层对高亲脂性溶质亲和力的重要决定因素，但对亲水性溶质的摄取没有影响。
