A novel in vitro percutaneous penetration model:: Evaluation of barrier properties with P-aminobenzoic acid and two of its derivatives
A novel in vitro percutaneous penetration model:: Evaluation of barrier properties with P-aminobenzoic acid and two of its derivatives
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DOI：
10.1007/s11095-006-9909-1
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发表时间：
2006-05-01
影响因子：
3.7
通讯作者：
Bouwstra, Joke
中科院分区：
文献类型：
--
作者：
de Jager, Miranda;Groenink, Wouter;Bouwstra, Joke
本研究的目的是评价角质层替代物（SCS）作为一种新型体外经皮渗透模型的实用性。SCS由应用于多孔基质上的合成角质层（SC）脂质（胆固醇、游离脂肪酸和特定神经酰胺）组成。的组合物，组织，和方向的脂质在SCS承担高度相似的SC中的细胞间屏障脂质。SCS的屏障完整性进行了评估，通过被动扩散研究，使用三种模型化合物具有不同的亲脂性。研究了脂质层厚度、渗透亲脂性和改变的脂质组成对屏障特性的影响，使用分离的人SC作为对照样品。对于所有三种模型化合物，具有12 μ m厚脂质层的SCS的渗透特性与人SC的渗透特性非常相似。脂质组成的改变，产生缺乏SC中存在的特征性长周期相的SCS伴随着2倍增加的渗透性。SCS提供了预测溶质通过人体皮肤渗透的有吸引力的工具。此外，由于其脂质组成可以改变，它们也可以作为患病皮肤的合适筛选模型。
The objective of this study was to evaluate the utility of a stratum corneum substitute (SCS) as a novel in vitro percutaneous penetration model. The SCS consists of synthetic stratum corneum (SC) lipids (cholesterol, free fatty acids, and specific ceramides) applied onto a porous substrate. The composition, organization, and orientation of lipids in the SCS bear high resemblance to that of the intercellular barrier lipids in SC.The barrier integrity of the SCS was evaluated by means of passive diffusion studies, using three model compounds with different lipophilicities. The effects of lipid layer thickness, permeant lipophilicity, and altered lipid composition on the barrier properties were investigated, using isolated human SC as a control sample.For all three model compounds, the permeability characteristics of the SCS with a 12-mu m-thick lipid layer closely resemble those of human SC. Modification of the lipid composition, generating an SCS that lacks the characteristic long periodicity phase as present in SC, was accompanied by a 2-fold increased permeability.The SCS offers an attractive tool to predict solute permeation through human skin. Moreover, as its lipid composition can be modified, they may also serve as a suitable screening model for diseased skin.