AN IN-VIVO EXPERIMENTAL-MODEL FOR EFFECTS OF TOPICAL RETINOIC ACID INHUMAN SKIN

An occlusive patch-test assay has been developed for assessment of top ical retinoid action in human epidermis. Previous work with this assay has demonstrated marked epidermal hyperplasia in skin treated with to pical all-trans-retinoic acid for 4 days and similar effects with the local irritant, sodium lauryl sulphate. To investigate the capabilitie s of this assay further, a time-course and dose-response were performe d with all-trans-retinoic acid, and a comparison made with sodium laur yl sulphate. At no time, between 1 and 4 days, could the clinical or h istological 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 aci d at concentrations from 0-001 to 0.025% dissolved in a 70% ethanol/30 % propylene glycol vehicle. All-trans-retinoic acid could be successfu lly differentiated from sodium lauryl sulphate at 2 days by virtue of its greater ability to increase epidermal thickness, spongiosis and gl ycosaminoglycan deposition. It appears that although all-trans-retinoi c acid and sodium lauryl sulphate produce similar epidermal histologic al changes at 4 days, significant differences at earlier time-points s uggest differing mechanisms of action. In addition, this in vivo human assay is able to provide potency ranking for doses of all-trans-retin oic acid, and may predict clinical efficacy of retinoids in improvemen t of acne and/or photodamage.