Tsai J-C, Shen L-C, Sheu H-M, Lu C-C
Institute of Clinical Pharmacy, College of Medicine, National Cheng Kung University, 1 University Road, 70101 Tainan, Taiwan.
Arch Dermatol Res. 2003 Aug;295(4):169-74. doi: 10.1007/s00403-003-0414-7. Epub 2003 Jul 1.
Prior studies in hairless mice have demonstrated that acute barrier disruption by acetone treatment increases the molecular weight (MW) cutoff of polyethylene glycol (PEG) penetration through the skin. The objective of the present study was to further investigate the dependence of permeability on MW with different forms of barrier disruption. A series of PEGs ranging in MW from near 300 to over 1000 Da were used to study the effects of tape stripping and sodium dodecyl sulfate (SDS) treatment on the MW permeability profiles of mouse skin in vitro. The 12-h percutaneous penetration of all the PEG 300, 600, and 1000 oligomers generally increased as a function of transepidermal water loss (TEWL) of the skin, either tape-stripped or SDS-treated. In addition, the total penetration of PEG oligomers across control skin, and skin tape-stripped and SDS-treated to different degrees of barrier disruption progressively decreased with increasing MW. There were no significant differences in the percutaneous penetration of the PEG oligomers between skin tape-stripped and SDS-treated to the same degree of barrier disruption. The penetration enhancement relative to control skin was more prominent with larger molecules. The MW cutoff for skin penetration increased with the degree of barrier disruption irrespective of the treatment applied, and was 986 Da (tape stripping) and 766 Da (SDS treatment) at TEWL levels in the range 10-20 g/m(2) per h in comparison with 414 Da for control skin. In accordance with previous findings in acetone-treated mouse skin, the results strongly suggest that, irrespective of the form of barrier disruption applied, not only higher amounts but also more varieties of chemicals (larger molecules) may penetrate skin with a compromised barrier than normal skin.
先前对无毛小鼠的研究表明,通过丙酮处理造成急性屏障破坏会增加聚乙二醇(PEG)透过皮肤的分子量(MW)截留值。本研究的目的是进一步研究在不同形式的屏障破坏情况下,渗透性对分子量的依赖性。使用一系列分子量范围从近300到超过1000 Da的PEG来研究胶带剥离和十二烷基硫酸钠(SDS)处理对小鼠皮肤体外MW渗透性曲线的影响。所有PEG 300、600和1000低聚物的12小时经皮渗透通常随着皮肤经表皮水分流失(TEWL)而增加,无论是胶带剥离的皮肤还是经SDS处理的皮肤。此外,PEG低聚物穿过对照皮肤、以及胶带剥离和SDS处理至不同程度屏障破坏的皮肤的总渗透量随着分子量增加而逐渐降低。在相同程度屏障破坏的胶带剥离皮肤和SDS处理皮肤之间,PEG低聚物的经皮渗透没有显著差异。相对于对照皮肤,较大分子的渗透增强更为显著。无论采用何种处理,皮肤渗透的MW截留值都随着屏障破坏程度增加而增加,在TEWL水平为10 - 20 g/m²每小时时,胶带剥离处理的为986 Da,SDS处理的为766 Da,而对照皮肤为414 Da。与先前在丙酮处理的小鼠皮肤中的发现一致,结果强烈表明,无论应用何种形式的屏障破坏,与正常皮肤相比,屏障受损的皮肤不仅可以渗透更多量的化学物质,而且可以渗透更多种类的化学物质(更大的分子)。