The natural function of the skin is to protect the body from unwanted influences from the environment. The main barrier of the skin is located in the outermost layer of the skin, the stratum corneum. Since the lipids regions in the stratum corneum form the only continuous structure, substances applied onto the skin always have to pass these regions. For this reason the organization in the lipid domains is considered to be very important for the skin barrier function. Due to the exceptional stratum corneum lipid composition, with long chain ceramides, free fatty acids and cholesterol as main lipid classes, the lipid phase behavior is different from that of other biological membranes. In stratum corneum crystalline phases are predominantly present, but most probably a subpopulation of lipids forms a liquid phase. Both the crystalline nature and the presence of a 13 nm lamellar phase are considered to be crucial for the skin barrier function. Since it is impossible to selectively extract individual lipid classes from the stratum corneum, the lipid organization has been studied in vitro using isolated lipid mixtures. These studies revealed that mixtures prepared with isolated stratum corneum lipids mimic to a high extent stratum corneum lipid phase behavior. This indicates that proteins do not play an important role in the stratum corneum lipid phase behavior. Furthermore, it was noticed that mixtures prepared only with ceramides and cholesterol already form the 13 nm lamellar phase. In the presence of free fatty acids the lattice density of the structure increases. In stratum corneum the ceramide fraction consists of various ceramide subclasses and the formation of the 13 nm lamellar phase is also affected by the ceramide composition. Particularly the presence of ceramide 1 is crucial. Based on these findings a molecular model has recently been proposed for the organization of the 13 nm lamellar phase, referred to as "the sandwich model", in which crystalline and liquid domains coexist. The major problem for topical drug delivery is the low diffusion rate of drugs across the stratum corneum. Therefore, several methods have been assessed to increase the permeation rate of drugs temporarily and locally. One of the approaches is the application of drugs in formulations containing vesicles. In order to unravel the mechanisms involved in increasing the drug transport across the skin, information on the effect of vesicles on drug permeation rate, the permeation pathway and perturbations of the skin ultrastructure is of importance. In the second part of this paper the possible interactions between vesicles and skin are described, focusing on differences between the effects of gel-state vesicles, liquid-state vesicles and elastic vesicles.

中文翻译：

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皮肤屏障的结构及其通过水泡制剂的调节。

皮肤的自然功能是保护身体免受环境的有害影响。皮肤的主要屏障位于皮肤的最外层，即角质层。由于角质层中的脂质区域形成唯一的连续结构，因此涂在皮肤上的物质必须始终通过这些区域。因此，脂质区域中的组织被认为对于皮肤屏障功能非常重要。由于角质层脂质的特殊组成，其中长链神经酰胺，游离脂肪酸和胆固醇为主要脂质类别，因此脂质相的行为不同于其他生物膜。在角质层中主要存在结晶相，但很可能脂质的亚群形成液相。晶体性质和13 nm层状相的存在都被认为对皮肤屏障功能至关重要。由于不可能从角质层中选择性地提取单个脂质类别，因此已经在体外使用分离的脂质混合物研究了脂质组织。这些研究表明，用分离的角质层脂质制备的混合物在很大程度上模拟了角质层脂质相的行为。这表明蛋白质在角质层脂质相行为中不发挥重要作用。此外，注意到仅用神经酰胺和胆固醇制备的混合物已经形成13 nm层状相。在游离脂肪酸的存在下，结构的晶格密度增加。在角质层中，神经酰胺级分由各种神经酰胺亚类组成，并且13纳米层状相的形成也受到神经酰胺成分的影响。特别是神经酰胺1的存在至关重要。基于这些发现，最近提出了用于组织13nm层状相的分子模型，称为“夹心模型”，其中结晶域和液相域共存。局部用药的主要问题是药物在角质层中的扩散率低。因此，已经评估了几种方法来临时和局部地增加药物的渗透率。方法之一是在含有囊泡的制剂中使用药物。为了阐明涉及增加药物在皮肤中运输的机制，关于囊泡对药物渗透率，渗透途径和皮肤超微结构扰动的影响的信息是重要的。在本文的第二部分中，描述了囊泡与皮肤之间可能的相互作用，着眼于凝胶状囊泡，液态囊泡和弹性囊泡的作用之间的差异。