Hadgraft Jonathan, Lane Majella E
Department of Pharmaceutics, The School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom.
Int J Pharm. 2009 May 21;373(1-2):1-3. doi: 10.1016/j.ijpharm.2009.02.007. Epub 2009 Feb 21.
The skin has a unique barrier to the ingress of hazardous materials and the egress of water. The barrier properties of the skin reside in the outer 15 microm, the stratum corneum, which has often been regarded as rather inert or even dead. The excellent barrier properties of this thin layer result from its structure which comprises of pentagonal or hexagonal corneocytes embedded in a lipid matrix. Corneocyte turnover and epidermal proliferation is controlled by desquamatory proteases and protease inhibitors in the epidermis. Disorders in barrier function and disruption of barrier homeostasis have been associated with changes in the expression patterns of epidermal serine proteases and variations in serine protease activity have also been identified at different body sites. The major route of permeation is around the corneocytes, therefore, the larger the corneocytes the longer the route for the permeation. Corneocyte size is dependent on the site on the body and this can be directly related to the permeability. For example, the face has thinner skin and the corneocyte size is smaller than the arm. This results in a shorter path for a drug to penetrate. Transepidermal water loss (TEWL) is a measure of the amount of water from within the skin to the external atmosphere. Rougier et al. showed that variations in corneocyte size at different anatomical sites were reflected in TEWL at these sites. The path length at different body sites was calculated using a simple geometric equation and a direct reciprocal relationship between the path length and TEWL was identified. A linear trend between cell size and cell layers at different sites is also evident in the data. Since higher protease activity should result in smaller corneocyte sizes and fewer cell layers, this in turn may be related to reported variations in enzyme activity at these sites.
皮肤对有害物质的侵入和水分的流失具有独特的屏障作用。皮肤的屏障特性存在于最外层的15微米，即角质层，角质层常被认为是相当惰性甚至是死的。这一薄层出色的屏障特性源于其结构，该结构由嵌入脂质基质中的五角形或六角形角质形成细胞组成。角质形成细胞的更新和表皮增殖受表皮中的脱屑蛋白酶和蛋白酶抑制剂控制。屏障功能障碍和屏障稳态破坏与表皮丝氨酸蛋白酶表达模式的变化有关，并且在不同身体部位也发现了丝氨酸蛋白酶活性的变化。渗透的主要途径是围绕角质形成细胞，因此，角质形成细胞越大，渗透途径越长。角质形成细胞的大小取决于身体部位，这可能与通透性直接相关。例如，面部皮肤较薄，角质形成细胞的大小比手臂小。这导致药物渗透的路径更短。经表皮水分流失（TEWL）是衡量皮肤内水分向外部大气流失量的指标。鲁吉尔等人表明，不同解剖部位角质形成细胞大小的变化反映在这些部位的TEWL中。使用简单的几何方程计算不同身体部位的路径长度，并确定路径长度与TEWL之间的直接反比关系。数据中不同部位的细胞大小与细胞层数之间的线性趋势也很明显。由于较高的蛋白酶活性应导致较小的角质形成细胞大小和较少的细胞层数，这反过来可能与这些部位报道的酶活性变化有关。
