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 combination 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% fatty acid/EtOH. The permeability coefficient of LHRH was significantly (p < 0.05) greater through EtOH, lauric acid/EtOH, palmitic acid/EtOH, oleic acid/EtOH, linoleic acid/EtOH, and linolenic acid/EtOH treated epidermis than the control (untreated epidermis). Iontophoresis further enhanced the permeability of LHRH (p < 0.05) through enhancer-pretreated epidermis in comparison with corresponding passive permeability. Among saturated fatty acids tested, 10% palmitic acid/iontophoresis showed 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 were more effective penetration enhancers when compared with octadecanoic acid. Among cis-octadecenoic acids in combination with EtOH, the greater iontophoretic permeability coefficient [(59.18 +/- 12.43) x 10(-4) cm/h] was obtained through linolenic acid treated epidermis, which was significantly greater (p < 0.05) than through saturated octadecanoic acid treated epidermis [(29.08 +/- 3.18) x 10(-4) cm/h]. Also, pretreatment of epidermis with 5% linolenic acid/propylene glycol (PG) resulted in greater (p < 0.05) iontophoretic flux of LHRH in comparison to 5% linolenic acid/EtOH. Furthermore, increases in the degree of unsaturation in octadecenoic acids did not produce corresponding increases in the degree of enhancement. Reversibility studies revealed that the postrecovery passive flux of LHRH through 5% linolenic acid in combination 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 epidermis).