Čižinauskas Vytis, Elie Nicolas, Brunelle Alain, Briedis Vitalis
Department of Clinical Pharmacy, Lithuanian University of Health Sciences, Sukilėlių pr. 13, 50166 Kaunas, Lithuania.
Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Univ. Paris-Sud, Université Paris-Saclay, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Biointerphases. 2017 Mar 2;12(1):011003. doi: 10.1116/1.4977941.
Linoleic, oleic, palmitoleic, palmitic, and stearic fatty acids (FAs) are commonly used in dermatological formulations. They differ by their structure, presence in the skin, and mode of application in pharmaceuticals and cosmetics compounding. These FAs are also known as chemical penetration enhancers, but their mechanisms of penetration enhancement and effect on barrier characteristics of the skin require additional study. In this study, the authors conducted an ex vivo analysis of the distribution of lipid components in the epidermis and dermis of human skin after applying individual FAs. The goal was to elucidate possible mechanisms of penetration enhancement and FA effects on barrier characteristics of the skin. FA penetration studies were conducted ex vivo on human skin and time-of-flight secondary ion mass spectrometry (TOF-SIMS) bioimaging analysis was performed to visualize and analyze distribution of FAs in skin sections. The current study demonstrated that TOF-SIMS imaging was effective in visualizing the distribution of linoleic, oleic, palmitoleic, palmitic, and stearic acid in the human skin ex vivo after the skin penetration experiment of individual FAs. The integration of the obtained TOF-SIMS images allowed a semiquantitative comparison of the effects induced by individual FA applications on the human skin ex vivo. FAs showed varying abilities to penetrate the skin and disorder the FAs within the skin, based on their structures and physicochemical properties. Linoleic acid penetrated the skin and changed the distribution of all the analyzed FAs. Skin treatment with palmitoleic or oleic acid increased the amounts of singular FAs in the skin. Penetration of saturated FAs was low, but it increased the detected amounts of linoleic acid in both skin layers. The results indicate that application of FAs on the skin surface induce redistribution of native FAs not only in the stratum corneum layer of epidermis but also in the lipid content of full epidermis and dermis layers. The results indicate that topically applied pharmaceutical products should be evaluated for potential chemical penetration enhancement and lipid component redistribution effects during formulation.
亚油酸、油酸、棕榈油酸、棕榈酸和硬脂酸常用于皮肤科制剂中。它们在结构、在皮肤中的存在情况以及在药物和化妆品配制中的应用方式上有所不同。这些脂肪酸也被称为化学渗透促进剂，但其渗透增强机制以及对皮肤屏障特性的影响仍需进一步研究。在本研究中，作者对涂抹单一脂肪酸后人体皮肤表皮和真皮中脂质成分的分布进行了体外分析。目的是阐明可能的渗透增强机制以及脂肪酸对皮肤屏障特性的影响。在人体皮肤上进行了脂肪酸渗透的体外研究，并采用飞行时间二次离子质谱（TOF-SIMS）生物成像分析来可视化和分析皮肤切片中脂肪酸的分布。当前研究表明，在单一脂肪酸皮肤渗透实验后，TOF-SIMS成像能够有效地在体外可视化人体皮肤中亚油酸、油酸、棕榈油酸、棕榈酸和硬脂酸的分布。对获得的TOF-SIMS图像进行整合，能够对单一脂肪酸涂抹于体外人体皮肤所产生的影响进行半定量比较。基于其结构和物理化学性质，脂肪酸显示出不同的穿透皮肤以及扰乱皮肤内脂肪酸的能力。亚油酸穿透皮肤并改变了所有分析脂肪酸的分布。用棕榈油酸或油酸处理皮肤会增加皮肤中单一脂肪酸的含量。饱和脂肪酸的渗透率较低，但会增加两层皮肤中检测到的亚油酸含量。结果表明，在皮肤表面涂抹脂肪酸不仅会导致表皮角质层中天然脂肪酸的重新分布，还会使整个表皮层和真皮层的脂质成分发生重新分布。结果表明，在制剂过程中，应评估局部应用的药品潜在的化学渗透增强和脂质成分重新分布效应。
