Mohammed Diar, Hirata Kazumasa, Hadgraft Jonathan, Lane Majella E
Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Eur J Pharm Sci. 2014 Jan 23;51:118-22. doi: 10.1016/j.ejps.2013.09.009. Epub 2013 Sep 21.
In order to overcome the skin's excellent barrier function formulation scientists often employ skin penetration enhancers (SPEs) in topical and transdermal formulations. The effects of these compounds on skin health is still not well understood at the molecular level. The aim of the present work was to probe the effects of some common SPEs on desquamatory protease activity in healthy skin. The SPEs studied were isopropyl myristate (IPM), propylene glycol, (PG), propylene glycol laurate (PGL) and Transcutol™ (TC). Occluded infinite doses of each SPE were applied to human volunteers for 24 h. Transepidermal water loss (TEWL) measurements were taken before and after application of SPEs. Tape strips were collected from the treated sites to determine protein content and the activity of two desquamatory proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7). TEWL values were also measured after tape stripping. PG was found to elevate both TEWL values and KLK7 activity to a significant extent (p<0.05). No significant effects were observed for the other SPEs. The ability of PG to alter the skin barrier at the macroscopic level and the influence of the molecule on protease activity reported here may have implications for its use in topical formulations used for the management of impaired skin barrier function such as atopic eczema or psoriasis.
为了克服皮肤出色的屏障功能,制剂科学家通常在局部和透皮制剂中使用皮肤渗透促进剂(SPEs)。这些化合物对皮肤健康的影响在分子水平上仍未得到充分了解。本研究的目的是探究一些常见的皮肤渗透促进剂对健康皮肤中脱屑蛋白酶活性的影响。所研究的皮肤渗透促进剂有肉豆蔻酸异丙酯(IPM)、丙二醇(PG)、月桂酸丙二醇酯(PGL)和Transcutol™(TC)。将每种皮肤渗透促进剂的封闭无限剂量应用于人类志愿者24小时。在应用皮肤渗透促进剂之前和之后测量经表皮水分流失(TEWL)。从处理部位收集胶带条以测定蛋白质含量以及两种脱屑蛋白酶激肽释放酶5(KLK5)和激肽释放酶7(KLK7)的活性。在胶带剥离后也测量经表皮水分流失值。发现丙二醇在很大程度上提高了经表皮水分流失值和激肽释放酶7的活性(p<0.05)。其他皮肤渗透促进剂未观察到显著影响。本文报道的丙二醇在宏观水平上改变皮肤屏障的能力以及该分子对蛋白酶活性的影响可能对其在用于管理受损皮肤屏障功能(如特应性皮炎或银屑病)的局部制剂中的应用具有启示意义。