Ceramide Profiling of Porcine Skin and Systematic Investigation of the Impact of Sorbitan Esters (SEs) on the Barrier Function of the Skin

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Hans Schoenfelder, Moritz Reuter, Dirk-Heinrich Evers, Michael E. Herbig and Dominique Jasmin Lunter*, 
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Abstract

The stratum corneum (SC) lipids provide the main barrier of the skin against the environment. Ceramides make up about half of the lipids by weight and are thus of particular interest. Emulsifiers are used in a multitude of topical formulations, e.g., to stabilize emulsions against coalescence. Investigations showed that some emulsifiers have the potential to impair skin barrier function. Sorbitan esters (SEs) are frequently used emulsifiers in pharmaceutical and cosmetic dermal formulations. Further, cholesterol and lecithin were used as natural alternatives. However, information on their impact on ceramides is very scarce. Thus, we first analyzed the SEs by LC-MS with regard to their composition. Then we developed an LC-MS method to identify and quantify the ceramides in porcine skin and subsequently investigated the impact of emulsifiers on the ceramide profile. Besides the LC-MS measurements, the effect of emulsifiers on the skin barrier function was investigated by trans-epidermal water loss (TEWL) measurements and confocal Raman spectroscopy (CRS). Throughout the experiments, water was used as a negative control and sodium lauryl sulfate (SLS) as a positive control. It was found that SEs are mixtures of mono-, di-, and triesters, partially with a complex fatty acid distribution. LC-MS measurements of the total ceramide content of the SC samples revealed the SE 60 and cholesterol-treated samples to be those showing the least ceramide depletion, implying a high skin tolerability in general. The TEWL measurements showed that SEs 40, 60, 80, and 120 showed no significant changes in skin barrier function. The lipid content, measured by CRS, was mostly decreased except for SE 120. Conformation, chain order, and SC thickness, also measured by CRS, showed no significant differences. These detailed investigations lead to the view that SEs are skin-friendly substances and can be used for topical applications, e.g., those commonly used to treat skin diseases.

猪皮肤神经酰胺谱分析及山梨糖酯对皮肤屏障功能影响的系统研究
角质层(SC)脂质提供皮肤对抗环境的主要屏障。神经酰胺约占脂质重量的一半,因此引起了人们的特别关注。乳化剂用于许多局部配方中,例如,稳定乳剂以防止聚结。调查显示,一些乳化剂有可能损害皮肤屏障功能。山梨醇酯(SEs)是常用的乳化剂在医药和化妆品的皮肤配方。此外,胆固醇和卵磷脂被用作天然替代品。然而,关于它们对神经酰胺的影响的信息非常少。因此,我们首先用LC-MS分析了se的组成。然后,我们开发了一种LC-MS方法来鉴定和定量猪皮中的神经酰胺,并随后研究了乳化剂对神经酰胺谱的影响。除LC-MS测量外,还通过经表皮水分损失(TEWL)测量和共聚焦拉曼光谱(CRS)研究了乳化剂对皮肤屏障功能的影响。在整个实验过程中,以水为阴性对照,以十二烷基硫酸钠(SLS)为阳性对照。结果发现,se是单酯、二酯和三酯的混合物,部分具有复杂的脂肪酸分布。SC样品的总神经酰胺含量的LC-MS测量显示,SE 60和胆固醇处理的样品显示出最少的神经酰胺消耗,这意味着通常具有较高的皮肤耐受性。TEWL测量显示,se40、60,80和120组皮肤屏障功能无明显变化。CRS法测定脂质含量,除SE 120外,其余均降低。构象、链序和SC厚度,也用CRS测量,没有显着差异。这些详细的调查表明,se是对皮肤友好的物质,可以用于局部应用,例如通常用于治疗皮肤病的物质。
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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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