Enhanced delivery of nalidixic acid through human skin via acyloxymethyl ester prodrugs

Abstract

Nalidixic acid has recently been suggested as a potentially useful agent for the treatment of psoriasis. In an attempt to improve the dermal delivery characteristics of nalidixic acid various esters of the compound were synthesized and assessed as prodrug forms for the parent drag. The esters studied include the methyl ester, a glycolamide ester and several acyloxylmethyl esters. Whereas the former two esters were only partly converted to the parent drug during diffusion through human skin samples, the acyloxymethyl derivatives were completely converted by enzymatic hydrolysis. Among the latter derivatives the butyryloxymethy) and the isobutyryloxymethyl esters showed a 5-6-fold enhanced delivery of nalidixic acid from both polar and apolar vehicles relative to application of nalidixic acid itself. The enhanced transport was suggested to be a result of the increased water and lipid solubilities of the ester derivatives in comparison to the parent drug. © 1989.