An in vivo experimental model for effects of topical retinoic acid in human skin.
An occlusive patch-test assay has been developed for assessment of topical retinoid action in human epidermis. Previous work with this assay has demonstrated marked epidermal hyperplasia in skin treated with topical all-trans-retinoic acid for 4 days and similar effects with the local irritant, sodium lauryl sulphate. To investigate the capabilities of this assay further, a time-course and dose-response were performed with all-trans-retinoic acid, and a comparison made with sodium lauryl sulphate. At no time, between 1 and 4 days, could the clinical or histological effects of 0.1% and 0.025% cream formulations of all-trans-retinoic acid be distinguished from each other. Epidermal hyperplasia was used to generate a 4-day dose-response for all-trans-retinoic acid at concentrations from 0.001 to 0.025% dissolved in a 70% ethanol/30% propylene glycol vehicle. All-trans-retinoic acid could be successfully differentiated from sodium lauryl sulphate at 2 days by virtue of its greater ability to increase epidermal thickness, spongiosis and glycosaminoglycan deposition. It appears that although all-trans-retinoic acid and sodium lauryl sulphate produce similar epidermal histological changes at 4 days, significant differences at earlier time-points suggest differing mechanisms of action. In addition, this in vivo human assay is able to provide potency ranking for doses of all-trans-retinoic acid, and may predict clinical efficacy of retinoids in improvement of acne and/or photodamage.
Griffiths
C E
CE
Department of Dermatology, University of Michigan Medical Center, Ann Arbor 48109-0314.
Finkel
L J
LJ
Tranfaglia
M G
MG
Hamilton
T A
TA
Voorhees
J J
JJ
D000287:Administration, Topical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D009779:Occlusive Dressings; D010328:Patch Tests / Q000379:methods*; D011897:Random Allocation; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*
D012967:Sodium Dodecyl Sulfate; D014212:Tretinoin