Ceramide analogue 14S24 selectively recovers perturbed human skin barrier.
BACKGROUND
Topical ceramide application is an effective therapeutic approach in skin disorders with disturbed barrier function, including atopic dermatitis and psoriasis.


OBJECTIVE
To evaluate ceramide analogue N-tetracosanoyl-(l)-serine tetradecyl ester (14S24) using a novel ex vivo model.


METHODS
Freshly excised human skin was disrupted by lipid extraction, tape stripping and sodium lauryl sulphate (SLS) treatment. Barrier perturbation was evaluated by the measurement of transepidermal water loss (TEWL), skin hydration and the penetration of model compound, theophylline (TH), assessed by microdialysis. The effect of topical 5% 14S24 was compared with a commercial formulation containing a skin lipid mixture (LR) and control formulation with no skin lipids (L).


RESULTS
Both LR and 14S24 produced significant recovery of TEWL and TH penetration in extracted and tape-stripped skin with 14S24 being significantly more effective. In SLS-treated skin, 14S24 decreased TEWL but not TH penetration; LR was inactive. L improved skin hydration but not barrier characteristics. Weak correlation between TEWL and TH penetration was observed in extracted and tape-stripped skin but not in SLS-treated skin.


CONCLUSIONS
Cutaneous microdialysis can serve as a useful tool for the evaluation of skin barrier recovery by topical formulations ex vivo whereas TEWL may not be an appropriate measure of skin barrier function in such studies. The excellent barrier repair activity of 14S24 could be beneficial in skin disorders with ceramide deficiency.
Vávrová
K
K
Centre for New Antivirals and Antineoplastics, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, 50005 Hradec Králové, Czech Republic. katerina.vavrova@faf.cuni.cz
Hrabálek
A
A
Mac-Mary
S
S
Humbert
P
P
Muret
P
P
D000328:Adult; D001834:Body Water / Q000378:metabolism; D002518:Ceramides / Q000494:pharmacology*; D003902:Detergents; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D017551:Microdialysis / Q000379:methods; D008875:Middle Aged; D012694:Serine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D012967:Sodium Dodecyl Sulfate; D012997:Solvents; D013806:Theophylline / Q000493:pharmacokinetics; D046509:Tissue Culture Techniques; D014870:Water Loss, Insensible / Q000187:drug effects*
D002518:Ceramides; D003902:Detergents; C527064:N-tetracosanoyl-(L)-serine tetradecyl ester; D012997:Solvents; D012967:Sodium Dodecyl Sulfate; D012694:Serine; D013806:Theophylline