Leiden/Amsterdam Center for Drug Research, Department of Drug Delivery Technology, University of Leiden, Leiden, The Netherlands.
Eur J Pharm Biopharm. 2011 Oct;79(2):334-42. doi: 10.1016/j.ejpb.2011.05.007. Epub 2011 May 30.
The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the barrier function. The main lipid classes in stratum corneum are ceramides, cholesterol, and free fatty acids. In previous publications, a lipid model was presented, referred to as the stratum corneum substitute (SCS), that closely mimics the SC lipid organization and SC barrier function. In the present study, we use the SCS to study the effect of changes in lipid organization on the lipid barrier function using benzoic acid as permeation compound. First, in the SCS, we increased the level of one of the three major lipid classes keeping the ratio between the other lipid classes constant. An increased cholesterol level resulted in an increase in phase-separated cholesterol and a reduction in the permeability. An increase in ceramide or free fatty acid level resulted in the formation of additional phases, but had no significant influence on the permeability. We also examined models that mimic selected changes in lipid composition reported for dry or diseased skin. The SCS that mimics the composition in recessive X-linked ichthyosis skin displayed a twofold increase in permeability. This increase is possibly related to the formation of an additional, less ordered phase in this model.
皮肤最上层的脂质，即角质层（SC），在屏障功能中起着重要作用。角质层中的主要脂质类包括神经酰胺、胆固醇和游离脂肪酸。在之前的出版物中，提出了一种脂质模型，称为角质层替代物（SCS），它可以很好地模拟 SC 的脂质组织和 SC 的屏障功能。在本研究中，我们使用 SCS 来研究脂质组织变化对脂质屏障功能的影响，以苯甲酸作为渗透化合物。首先，在 SCS 中，我们在保持其他脂质类比例不变的情况下，增加了三种主要脂质类中的一种的水平。胆固醇水平的增加导致相分离胆固醇的增加和通透性的降低。神经酰胺或游离脂肪酸水平的增加导致形成额外的相，但对通透性没有显著影响。我们还研究了模拟干性或病理性皮肤中脂质组成变化的模型。模拟隐性 X 连锁鱼鳞病皮肤组成的 SCS 显示通透性增加了两倍。这种增加可能与该模型中形成额外的、无序程度较低的相有关。
