Transport of Ionic Species in Skin: Contribution of Pores to the Overall Skin Conductance

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Abstract
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 µA/cm2). In the first method, the counter-directional iontophoretic transport of Fe(CN)64− 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)64− 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%.