Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy.

OBJECTIVE AND DESIGN: The skin retention and penetration characteristics of copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate were evaluated in vitro in order to assess the potential for its transdermal delivery as anti-inflammatory agent. MATERIALS AND METHODS: Flow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. Copper as a tripeptide was applied on isolated stratum corneum, on heat-separated epidermis and on dermatomed skin. Receptor fluid collected over 48 h in 4 h intervals was analyzed by inductively coupled plasma mass spectrometry for copper in tissues and receptor fluid. RESULTS: The permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 μg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 82 ± 8.1 μg/cm(2) of copper were retained there as depot. CONCLUSIONS: Applied tansdermally as the tripeptide on human skin ex vivo, copper permeated the skin and was also retained in skin tissue in amounts potentially effective for the treatment of inflammatory diseases.