TRANSPORT OF IONIC SPECIES IN SKIN - CONTRIBUTION OF PORES TO THE OVERALL SKIN-CONDUCTANCE

Two methods are reported that allow visualization of high conductance paths in skin at current densities typically used during clinical iont ophoretic drug delivery (10-200 muA/cm2). In the first method, the cou nter-directional iontophoretic transport of Fe(CN)6(4-) and Fe3+ acros s skin results in the precipitation of colloidal prussian blue, Fe4[Fe (CN)6]3, at sites of high iontophoretic flux. The appearance of locali zed deposits of Fe4[Fe(CN)6]3 is recorded by video microscopy and used to document the activation of low-resistance paths. In the second met hod, the ionic flux of Fe(CN)6(4-) through pores is directly imaged by scanning electrochemical microscopy (SECM). Both methods demonstrate that the iontophoretic flux across skin is highly localized. Activatio n of low-resistance pores in hairless mouse skin is shown to occur dur ing iontophoresis. The spatial density of current carrying pores incre ases from 0 to 100-600 pores/cm2 during the first 30-60 min of iontoph oresis. At longer times, the active pore density approaches a quasi-st eady-state value that is proportional to the applied current density. The total conductance of the skin is proportional to the number of por es, consistent with a model of conduction in skin that is comprised of low-resistivity pores in parallel with a high-resistivity bulk phase. The contribution of pores to the total skin conductance during iontop horesis increases from an initial value of 0-5% to a quasi-steady-stat e value of 50-95%.