Iontophoretic delivery of 5-fluorouracil through excised human stratum corneum

The objective of this study was to determine the effects of ionization, current density and penetration enhancers on the iontophoretic delivery of 5-fluorouracil (5-FU) through excised human stratum corneum (HSC). The iontophoretic (cathodal) transport of 5-FU was assessed in vitro at three physiologically relevant pH values of 5.0, 7.4 and 8.0, at various levels of current density ranging between 0.15 to 0.98 mA/cm2, and in the presence of suitable penetration enhancers, namely Azone(®) (AZ), lauryl alcohol (LA), and isopropyl myristate (IPM). The steady-state flux at constant current density (0.47 mA/cm(2)) was increased by　approximately 19, 10 and 27 fold at pH 5, 7.4 and 8.0, respectively. The effect of current density at pH 7.4 exhibited a linear correlation between current density and steady-state flux (r = 0.98, p = 0.002), which indicates the potential of iontophoresis for controlled transdermal delivery of 5-FU. The combination of cathodal iontophoresis with IPM produced an additive enhancement which may be attributed to aggravated skin perturbation effect and increased skin conductivity. Other enhancers such as AZ and LA produced negative or no further enhancement respectively, when used in conjunction with cathodal iontophoresis. It may be therefore concluded that pH and current density play critical role during iontophoretic delivery of 5-FU, and combination of a chemical penetration enhancer and iontophoresis can not be always viewed as a synergistic strategy which should be evaluated on a case-by-case basis for each drug candidate/enhancer combination.