Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Int J Pharm. 2013 Jan 30;441(1-2):192-201. doi: 10.1016/j.ijpharm.2012.11.043. Epub 2012 Dec 5.
Niacinamide-containing moisturisers are known be efficacious in alleviating dry skin conditions and improving stratum corneum (SC) barrier function. However, the mechanisms of action of niacinamide at the molecular level in the SC are still not well understood. Previously, we have reported the development of novel methods to probe SC barrier properties in vivo. The aim of the present study was to characterise changes in Trans Epidermal Water Loss (TEWL), corneocyte surface area and maturity, selected protease activities and SC thickness after repeated application of a simple vehicle containing niacinamide. A commercial formulation was also included as a reference. The left and right mid-volar forearms of 20 healthy volunteers were used as study sites, to which topical formulations were applied twice daily for 28 days. After successive tape-stripping, corneocyte maturity and surface area were assessed. In addition, activity of the desquamatory kallikrein (KLK) protease enzymes KLK5 and KLK7, and tryptase and plasmin (implicated in inflammatory process) were measured using a fluorogenic probe assay. The amount of protein removed and TEWL were also recorded. SC thickness before and after treatment was determined using Confocal Raman Spectroscopy (CRS). Overall (i) corneocyte maturity and surface area decreased with increasing number of tape strips, (ii) activity of both the desquamatory and inflammatory enzymes was highest in the outer layers of the SC and decreased with depth (iii) TEWL increased as more SC layers were removed. Furthermore, areas treated with formulations containing niacinamide were significantly different to pre-treatment baseline and untreated/vehicle-control treated sites, with larger and more mature corneocytes, decreased inflammatory activity, decreased TEWL and increased SC thickness. These data (a) confirm the utility of measures and metrics developed previously for the non-invasive assay of SC barrier function, (b) present an holistic picture of a SC compartment managing barrier function through dynamic optimisation of pathlength and quality of building materials used, and (c) shed new light on niacinamide as a topical formulation adjunct with unique SC barrier-augmentation properties.
烟酰胺保湿剂已被证实可有效缓解皮肤干燥，并改善角质层（SC）屏障功能。然而，烟酰胺在 SC 中的分子水平作用机制仍不清楚。此前，我们已经开发出了新的方法来探测 SC 屏障特性。本研究的目的是研究含有烟酰胺的简单载体重复应用后，经表皮水分丢失（TEWL）、角质细胞表面积和成熟度、特定蛋白酶活性以及 SC 厚度的变化。同时也包括了一种商业制剂作为参考。将 20 名健康志愿者的左右中侧前臂作为研究部位，每天两次将局部制剂涂抹于这些部位，连续 28 天。连续进行胶带撕除后，评估角质细胞成熟度和表面积。此外，还使用荧光探针测定了去角质激肽（KLK）蛋白酶 KLK5 和 KLK7 的活性以及类胰蛋白酶和纤溶酶（参与炎症过程）的活性。还记录了去除的蛋白质量和 TEWL。使用共聚焦拉曼光谱（CRS）测定 SC 厚度。结果表明：（i）随着胶带撕除次数的增加，角质细胞成熟度和表面积减小；（ii）无论是去角质酶还是炎症酶的活性，在 SC 的外层最高，随着深度的增加而降低；（iii）TEWL 随着 SC 层的去除而增加。此外，与预处理基线和未处理/载体对照处理部位相比，用含有烟酰胺的制剂处理的区域差异显著，具有更大和更成熟的角质细胞、炎症活性降低、TEWL 降低和 SC 厚度增加。这些数据（a）证实了之前开发的用于非侵入性 SC 屏障功能检测的措施和指标的实用性；（b）呈现了 SC 隔室通过对使用的路径长度和建筑材料质量的动态优化来管理屏障功能的整体情况；（c）揭示了烟酰胺作为一种具有独特 SC 屏障增强特性的局部制剂辅料的新作用。
