Enhanced transdermal delivery of phenylalanyl-glycine by chemical modification with various fatty acids.

We synthesized three novel lipophilic derivatives of phenylalanyl-glycine (Phe-Gly), C4-Phe-Gly, C6-Phe-Gly and C8-Phe-Gly by chemical modification with butyric acid (C4), caproic acid (C6) and octanoic acid (C8). The effect of the acylation on the stability, permeability and accumulation of Phe-Gly in the skin was investigated by in vitro studies. The stability of Phe-Gly in skin homogenates was low, but was significantly improved by the acylation.