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

Electroporation, the creation of transient, enhanced membrane permeability using short duration (microseconds to millisecond) electrical pulses, can be used to increase transdermal drug delivery. The effect of an (electroporative) electric pulse (1000 V, tau=5 msec) on the iontophoretic transport of LHRH through human skin was studied in vitro. Fluxes achieved with and without a pulse under different current densities (0- 4 mA/cm(2)) were compared. The results indicated that the application of a single pulse prior to iontophoresis consistently yielded higher fluxes (5-10 times the corresponding iontophoretic flux). For example, 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 density studied, the LHRH flux decreased after iontophoresis, approaching pre-treatment values. The results show that electroporation can significantly and reversibly increase the flux of LHRH through human skin. These results also indicate the therapeutic utility of using electroporation for enhanced transdermal transport.