LEO Pharma, Department of DMPK and Safety, Industriparken 55, 2750 Ballerup, Denmark; Leiden/Amsterdam Center for Drug Research (LACDR), Department of Drug Delivery Technology, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Int J Pharm. 2013 Nov 30;457(1):275-82. doi: 10.1016/j.ijpharm.2013.08.086. Epub 2013 Sep 10.
Lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier properties. The main lipid classes are ceramides, cholesterol and free fatty acids. In previous studies a stratum corneum substitute (SCS) was developed, solely prepared from the SC lipids. The SCS mimics the lipid barrier properties of SC very closely. The present study aimed to design a psoriasis SCS (PS-SCS) mimicking several aspects of the lipid composition in SC from psoriasis patients. This PS-SCS showed a different lipid organization than SCS. The main differences were a reduced presence of an orthorhombic packing and an increased level of crystalline cholesterol. These changes resulted in lower flux of hydrocortisone across PS-SCS than across SCS and SC, which was most likely attributed to the higher level of phase separated crystalline cholesterol in PS-SCS. As propylene glycol (PG) is often used in dermatological formulations, in subsequent studies the interaction of PG with SC and SCS membranes was also investigated. These studies revealed that PG increased the permeability of hydrocortisone, mainly by selectively extracting cholesterol from SCS membranes and SC. This may play an important role in the penetration enhancing effect of PG.
皮肤最上层的脂质，即角质层（SC），在皮肤屏障特性中起着重要作用。主要的脂质类包括神经酰胺、胆固醇和游离脂肪酸。在之前的研究中，开发了一种仅由 SC 脂质组成的角质层替代物（SCS）。SCS 非常接近地模拟了 SC 的脂质屏障特性。本研究旨在设计一种模仿银屑病患者 SC 中脂质组成的多个方面的银屑病角质层替代物（PS-SCS）。与 SCS 相比，这种 PS-SCS 的脂质组织呈现出不同的特点。主要差异在于正交堆积的存在减少和结晶胆固醇的水平增加。这些变化导致 PS-SCS 中氢化可的松的通量低于 SCS 和 SC，这很可能归因于 PS-SCS 中分离的结晶胆固醇水平较高。由于丙二醇（PG）常用于皮肤科制剂中，因此在随后的研究中还研究了 PG 与 SC 和 SCS 膜的相互作用。这些研究表明，PG 通过选择性地从 SCS 膜和 SC 中提取胆固醇，增加了氢化可的松的通透性。这可能在 PG 的渗透增强作用中起着重要作用。
