Hatta Ichiro, Nakazawa Hiromitsu, Ohta Noboru, Uchino Tomonobu, Yanase Kaori
Kaori YanaseDepartment of Research, Nagoya Industrial Science Research Institute.
School of Science and Technology, Kwansei Gakuin University.
J Oleo Sci. 2021 Sep 4;70(9):1181-1199. doi: 10.5650/jos.ess21159. Epub 2021 Aug 6.
Studies on the effectiveness of substances such as drugs and cosmetics that act on the skin require structural evidence at the molecular level in the stratum corneum to clarify their interaction with intercellular lipid and soft keratin. For this purpose, when applying the substances to the stratum corneum X-ray diffraction experiment is one of the powerful tools. To detect minute structural changes in a stratum corneum sample, using a "solution cell", dynamic synchrotron X-ray diffraction measurements were performed when applying aqueous solution of the substances to the stratum corneum: (1) It was found that a surfactant, sodium dodecyl sulfate, significantly disrupted the long-period lamellar structure. (2) To study the effects of water, structural modifications of the short-period lamellar structure and the soft keratin in corneocytes were measured as a function of time. At the initial water content of 15 wt%, the spacings of the short-period lamellar structure and the soft keratin increased toward those at the water content of 25 wt%, that is a key water content in the stratum corneum. (3) Nanoparticles composed of assembly of amphiphilic molecules are one of the leading pharmaceutical formulations. When the nanoparticles were applied, a new assembly of amphiphilic molecules originated from the nanoparticle appeared. This phenomenon suggests that the formation of the new assembly at the surface of skin is concerned with the release of the drug from the nanoparticles. (4) When ethanol was applied to the stratum corneum, only the liquid state in the intercellular lipid matrix was dissolved. After the removal of ethanol from this stratum corneum, the ordered hydrocarbon-chain packing structures appeared. From this fact we would propose that the liquid state region is the main pathway for hydrophobic drugs with a small molecular weight in connection with the so-called 500 Da rule. Here, not only the technique but also the background to these studies and the characteristic results obtained from these studies are explained.
对作用于皮肤的药物和化妆品等物质的有效性研究需要在分子水平上获得角质层的结构证据,以阐明它们与细胞间脂质和软角蛋白的相互作用。为此,在将这些物质应用于角质层时,X射线衍射实验是一种强大的工具。为了检测角质层样品中的微小结构变化,使用“溶液池”,在将物质的水溶液应用于角质层时进行了动态同步加速器X射线衍射测量:(1)发现一种表面活性剂十二烷基硫酸钠显著破坏了长周期层状结构。(2)为了研究水的影响,测量了短周期层状结构和角质形成细胞中软角蛋白的结构变化随时间的函数关系。在初始水含量为15 wt%时,短周期层状结构和软角蛋白的间距朝着水含量为25 wt%时的间距增加,25 wt%是角质层中的关键水含量。(3)由两亲分子组装而成的纳米颗粒是主要的药物制剂之一。当应用纳米颗粒时,出现了源自纳米颗粒的两亲分子新组装体。这种现象表明皮肤表面新组装体的形成与药物从纳米颗粒中的释放有关。(4)当将乙醇应用于角质层时,仅细胞间脂质基质中的液态被溶解。从该角质层中去除乙醇后,出现了有序的烃链堆积结构。基于这一事实,我们提出液态区域是与所谓的500 Da规则相关的小分子疏水性药物的主要途径。在此,不仅解释了这些研究的技术,还解释了这些研究的背景以及从这些研究中获得的特征性结果。