Percutaneous penetration of methylglyoxal bis(guanylhydrazone): effects on hairless mouse epidermis in vivo.

Topical methylglyoxal bis(guanylhydrazone) (MGBG) previously has been shown to produce partial clinical improvement in psoriasis. To enhance therapeutic activity, studies were undertaken to optimize MGBG percutaneous penetration in vitro and to study biochemical changes related to epidermal proliferation in vivo. MGBG penetration in saline, Vehicle N, decylmethylsulfoxide, and N-methylpyrrolidone was determined in normal human skin in vitro. Maximum penetration was obtained with 10% MGBG in Vehicle N (3 micrograms/h/cm2). Both topical and systemic MGBG resulted in increased levels of S-adenosyl-L-methionine decarboxylase, suggesting an extended half-life as a consequence of MGBG binding. Topical treatment with 10% MGBG in Vehicle N also resulted in decreased epidermal polyamine levels. The changes in polyamine metabolism were also associated with inhibition of epidermal DNA synthesis. These studies suggest that this topical MGBG formulation may be a candidate for use in the treatment of psoriasis and other hyperproliferative cutaneous diseases associated with increased polyamine synthesis.