title: Transport of ionic species in skin: contribution of pores to the overall skin conductance.
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 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%.
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis 55455.
authors.forename: E R
authors.initials: ER
authors.lastname: Scott
authors.forename: A I
authors.initials: AI
authors.lastname: Laplaza
authors.forename: H S
authors.initials: HS
authors.lastname: White
authors.forename: J B
authors.initials: JB
authors.lastname: Phipps
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004563:Electrochemistry; D005295:Ferrocyanides / Q000493:pharmacokinetics; D005296:Ferrous Compounds / Q000493:pharmacokinetics; D005712:Galvanic Skin Response / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007478:Iontophoresis; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D012867:Skin / Q000033:anatomy & histology / Q000378:metabolism*
chemical_list: D005295:Ferrocyanides; D005296:Ferrous Compounds; C000170:ferric ferrocyanide