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.