EFFECT OF ELECTROPORATION ON TRANSDERMAL IONTOPHORETIC DELIVERY OF LUTEINIZING-HORMONE-RELEASING HORMONE (LHRH) IN-VITRO

Electroporation, the creation of transient, enhanced membrane permeabi lity using short duration (microseconds to millisecond) electrical pul ses, can be used to increase transdermal drug delivery. The effect of an (electroporative) electric pulse (1000 V, tau=5 msec) on the iontop horetic transport of LHRH through human skin was studied in vitro. Flu xes achieved with and without a pulse under different current densitie s (0- 4 mA/cm(2)) were compared. The results indicated that the applic ation of a single pulse prior to iontophoresis consistently yielded hi gher fluxes (5-10 times the corresponding iontophoretic flux). For exa mple, at 0.5 mA/cm(2) fluxes were 0.27+/-0.08 and 1.62+/-0.05 mu g/hr/ cm(2) without and with the pulse, respectively. At each current densit y studied, the LHRH flux decreased after iontophoresis, approaching pr e-treatment values. The results show that electroporation can signific antly and reversibly increase the flux of LHRH through human skin. The se results also indicate the therapeutic utility of using electroporat ion for enhanced transdermal transport.