Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers
Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers
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DOI：
10.1046/j.1523-1747.2003.12131.x
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发表时间：
2003-05-01
影响因子：
6.5
通讯作者：
Roberts, MS
中科院分区：
文献类型：
--
作者：
Cross, SE;Magnusson, BM;Roberts, MS
为了建立溶质亲脂性和皮肤渗透（包括流量和浓度行为）之间的关系，我们研究了一系列的同源醇（C2-C10）的体外渗透和膜浓度的水溶液局部应用于人表皮，全层和真皮膜。在渗透过程中，分别测定每种醇在供体溶液、角质层、活表皮、真皮和受体相隔室之间的分配/分布，并分离至每种组织类型的分离样品。比较每种膜的最大通量和渗透系数，并根据通量/浓度数据以及每种膜类型的相关组织阻力（渗透系数的倒数）估计酒精扩散率。渗透系数随着对C8醇（辛醇）亲脂性的增加而增加，而对C10醇（癸醇）没有进一步增加。Log媒介物：角质层分配系数与logP相关，并且每个组织层中的醇浓度似乎随着亲脂性而增加。在三种膜中，较小的极性醇的扩散率没有测量到差异;然而，较大的亲脂性溶质显示出较慢的扩散率值。该研究表明，真皮可能是一个比最初认为的亲脂性更强的环境，并且可以仅根据其亲脂性的知识来估计较小的非离子化溶质在局部应用部位下方的局部组织中的分布。
In order to establish the relationship between solute lipophilicity and skin penetration (including flux and concentration behavior), we examined the in vitro penetration and membrane concentration of a series of homologous alcohols (C2-C10) applied topically in aqueous solutions to human epidermal, full-thickness, and dermal membranes. The partitioning/distribution of each alcohol between the donor solution, stratum corneum, viable epidermis, dermis, and receptor phase compartments was determined during the penetration process and separately to isolated samples of each tissue type. Maximum flux and permeability coefficients are compared for each membrane and estimates of alcohol diffusivity are made based on flux/concentration data and also the related tissue resistance (the reciprocal of permeability coefficient) for each membrane type. The permeability coefficient increased with increasing lipophilicity to alcohol C8 (octanol) with no further increase for C10 (decanol). Log vehicle:stratum corneum partition coefficients were related to logP , and the concentration of alcohols in each of the tissue layers appeared to increase with lipophilicity. No difference was measured in the diffusivity of smaller more polar alcohols in the three membranes; however, the larger more lipophilic solutes showed slower diffusivity values. The study showed that the dermis may be a much more lipophilic environment than originally believed and that distribution of smaller nonionized solutes into local tissues below a site of topical application may be estimated based on knowledge of their lipophilicity alone.