SYNERGISTIC EFFECT OF IONTOPHORESIS AND A SERIES OF FATTY-ACIDS ON LHRH PERMEABILITY THROUGH PORCINE SKIN

The effect of chemical penetration enhancers (e.g., fatty acids) in co mbination with iontophoresis was examined on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through porcine skin. Porcine epidermis was pretreated with either ethanol (EtOH) or 10% fa tty acid/EtOH. The permeability coefficient of LHRH was significantly (p < 0.05) greater through ROH, lauric acid/EtOH, palmitic acid/EtOH, oleic acid/EtOH, linoleic acid/EtOH, and linolenic acid/EtOH treated e pidermis than the control (untreated epidermis). lontophoresis further enhanced the permeability of LHRH (p < 0.05) through enhancer-pretrea ted epidermis in comparison with corresponding passive permeability. A mong saturated fairy acids tested, 10% palmitic acid/iontophoresis sho wed the highest permeability coefficient [(59.52 +/- 2.40) x 10(-4) cm /h], which was approximately 16-fold higher than that of the control [ (3.57 +/- 0.41) x 10(-4) cm/h]. Unsaturated cis-octadecenoic acids wer e more effective penetration enhancers when compared with octadecanoic acid. Among cis-octadecenoic acids in combination with EtOH, the grea ter iontophoretic permeability coefficient [(59.18 +/- 12.43) x 10(-4) cm/h] was obtained through linolenic acid treated epidermis, which wa s significantly greater (p < 0.05) than through saturated octadecanoic acid treated epidermis [(29.08 +/- 3.18) x 10(-4) cm/h]. Also, pretre atment of epidermis with 5% linolenic acid/propylene glycol (PG) resul ted in greater Gt,< 0.05) iontophoretic flux ct LHRH in comparison to 5% linolenic acid/EtOH. Furthermore, increases in the degree of unsatu ration in octadecenoic acids did not produce corresponding increases i n the degree of enhancement. Reversibility studies revealed that the p ostrecovery passive flux of LHRH through 5% linolenic acid in combinat ion with EtOH or PG/iontophoresis treated epidermis was significantly (p < 0.05) reduced than the prerecovery value but could not completely recover to the baseline flux (i.e., flux of LHRH through untreated ep idermis).