Influence of skin penetration enhancers on skin barrier function and skin protease activity.
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.
Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Diar
D
Mohammed
Kazumasa
K
Hirata
Jonathan
J
Hadgraft
Majella E
ME
Lane
D000279:Administration, Cutaneous; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000494:pharmacology*; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D014867:Water / Q000378:metabolism
D005079:Excipients; D014867:Water; D010447:Peptide Hydrolases; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins
Barrier function; Propylene glycol; Protease; Skin penetration enhancers; Transepidermal water loss