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 iontophoretic drug delivery (10-200 microA/cm2). In the first method, the counter-directional iontophoretic transport of Fe(CN)6(4-) and Fe3+ across skin results in the precipitation of colloidal prussian blue, Fe4[Fe(CN)6]3, at sites of high iontophoretic flux. The appearance of localized 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 method, 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. Activation of low-resistance pores in hairless mouse skin is shown to occur during iontophoresis. The spatial density of current carrying pores increases from 0 to 100-600 pores/cm2 during the first 30-60 min of iontophoresis. At longer times, the active pore density approaches a quasi-steady-state value that is proportional to the applied current density. The total conductance of the skin is proportional to the number of pores, 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 iontophoresis increases from an initial value of 0-5% to a quasi-steady-state value of 50-95%.