Although, drugs are required in the various skin compartments such as viable epidermis, dermis, or hair follicles, to efficiently treat skin diseases, drug delivery into and across the skin is still challenging. An improved understanding of skin barrier physiology is mandatory to optimize drug penetration and permeation. The various barriers of the skin have to be known in detail, which means methods are needed to measure their functionality and outside-in or inside-out passage of molecules through the various barriers. In this review, we summarize our current knowledge about mechanical barriers, i.e., stratum corneum and tight junctions, in interfollicular epidermis, hair follicles and glands. Furthermore, we discuss the barrier properties of the basement membrane and dermal blood vessels. Barrier alterations found in skin of patients with atopic dermatitis are described. Finally, we critically compare the up-to-date applicability of several physical, biochemical and microscopic methods such as transepidermal water loss, impedance spectroscopy, Raman spectroscopy, immunohistochemical stainings, optical coherence microscopy and multiphoton microscopy to distinctly address the different barriers and to measure permeation through these barriers in vitro and in vivo.

中文翻译：

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皮肤药物输送中的皮肤障碍：必须克服哪些障碍以及我们如何测量它们？


尽管为了有效治疗皮肤病，各种皮肤区室（例如存活的表皮、真皮或毛囊）都需要药物，但将药物输送到皮肤内和穿过皮肤仍然具有挑战性。为了优化药物的渗透和渗透，必须提高对皮肤屏障生理学的了解。必须详细了解皮肤的各种屏障，这意味着需要方法来测量它们的功能以及分子从外到内或从内到外穿过各种屏障的通道。在这篇综述中，我们总结了目前关于毛囊间表皮、毛囊和腺体中的机械屏障（即角质层和紧密连接）的知识。此外，我们讨论了基底膜和真皮血管的屏障特性。描述了特应性皮炎患者皮肤中发现的屏障改变。最后，我们批判性地比较了几种物理、生化和微观方法的最新适用性，例如经皮失水、阻抗谱、拉曼光谱、免疫组织化学染色、光学相干显微镜和多光子显微镜，以明确解决不同的障碍并测量在体外和体内渗透通过这些屏障。