Theory of electrical creation of aqueous pathways across skin transport barriers

Experimental studies have shown that application of electrical pulses to hu man skin that result in U-skin > 30 V for durations of about 1 ms or longer causes a large decrease in electrical resistance within microseconds, foll owed in seconds by an increase in molecular transport of water-soluble mole cules. Local transport regions (LTRs), within which molecular transport is concentrated, mostly form away from the skin's appendages and rete pegs. Th eoretical attempts to explain this behavior involve electrically created aq ueous pathways ("pores"). For short (about 1 ms) "high voltage" (HV) pulses leading to about U-skin > 50 V, it was hypothesized that such pulses cause electroporation of the multilamellar lipid bilayer membranes of the skin's stratum corneum (SC). Much of the present experimental evidence supports t he more specific hypothesis that such pulses create "straight through aqueo us pathways", mostly within LTRs, that perforate the SC Lipid bilayers and pass through the interiors of hydrated corneocytes. Theoretical estimates o f the localized heating within LTRs predict relatively small temperature ri ses. The theory of LTR formation is incomplete, with both stochastic and de terministic models under consideration. Moderate voltage (MV) pulses leadin g to about 5<U-skin<50 V, are consistent with appendageal activation and el ectroporation. The largest molecular fluxes occur for HV pulses, for which theory predicts large numbers of straight-through aqueous pathways. Both ap pendageal and stratum corneum electroporation are different from iontophore sis, which occurs at U-skin <5 V. (C) 1999 Elsevier Science B.V. All rights reserved.