Bouwstra J A, Gooris G S, Dubbelaar F E, Ponec M
Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
J Lipid Res. 2001 Nov;42(11):1759-70.
The lipid regions in the outermost layer of the skin (stratum corneum) form the main barrier for diffusion of substances through the skin. In this layer the main lipid classes are ceramides, cholesterol (CHOL), and FFA. Previous studies revealed a coexistence of two crystalline lamellar phases with periodicities of approximately 13 nm (referred to as long periodicity phase) and 6 nm (short periodicity phase). Additional studies showed that lipid mixtures prepared with isolated pig ceramides (pigCER) mimic lipid phase behavior in stratum corneum closely. Because the molecular structure of pigCER differs in some important aspects from that of human ceramides (HCER), in the present study the phase behavior of mixtures prepared with HCER has been examined. Phase behavior studies of mixtures based on HCER revealed that in CHOL:HCER mixtures the long periodicity phase dominates. In the absence of HCER1 the short periodicity phase is dominant. Addition of FFA promotes the formation of the short periodicity phase and induces a transition from a hexagonal sublattice to an orthorhombic sublattice. Furthermore, the presence of FFA promotes the formation of a liquid phase. Finally, cholesterol sulfate, a minor but important lipid in the stratum corneum, reduces the amount of cholesterol that phase separates in crystalline domains. From these observations it can be concluded that the phase behavior of mixtures prepared from HCER differs in some important aspects from that prepared from pigCER. The most prevalent differences are the following: i) the addition of FFA promotes the formation of the short periodicity phase; and ii) liquid lateral packing is obviously present in CHOL:HCER:FFA mixtures. These changes in phase behavior might be due to a larger amount of linoleic acid moiety in HCER mixtures compared with that in pigCER mixtures.
皮肤最外层（角质层）中的脂质区域构成了物质通过皮肤扩散的主要屏障。在这一层中，主要的脂质类别是神经酰胺、胆固醇（CHOL）和游离脂肪酸（FFA）。先前的研究揭示了两种具有约13 nm周期（称为长周期相）和6 nm周期（短周期相）的结晶层状相共存。进一步的研究表明，用分离的猪神经酰胺（pigCER）制备的脂质混合物紧密模拟了角质层中的脂质相行为。由于pigCER的分子结构在一些重要方面与人类神经酰胺（HCER）不同，因此在本研究中，对用HCER制备的混合物的相行为进行了研究。基于HCER的混合物的相行为研究表明，在CHOL:HCER混合物中，长周期相占主导。在没有HCER1的情况下，短周期相占主导。添加FFA促进短周期相的形成，并诱导从六方亚晶格向正交亚晶格的转变。此外，FFA的存在促进液相的形成。最后，硫酸胆固醇是角质层中一种含量较少但很重要的脂质，它减少了在结晶域中相分离的胆固醇量。从这些观察结果可以得出结论，由HCER制备的混合物的相行为在一些重要方面与由pigCER制备的混合物不同。最主要的差异如下：i）添加FFA促进短周期相的形成；ii）在CHOL:HCER:FFA混合物中明显存在液体侧向堆积。相行为的这些变化可能是由于HCER混合物中亚油酸部分的含量比pigCER混合物中的多。
