Theory of electrical creation of aqueous pathways across skin transport barriers.

Experimental studies have shown that application of electrical pulses to human 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, followed in seconds by an increase in molecular transport of water-soluble molecules. Local transport regions (LTRs), within which molecular transport is concentrated, mostly form away from the skin's appendages and rete pegs. Theoretical attempts to explain this behavior involve electrically created aqueous 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 the more specific hypothesis that such pulses create "straight through aqueous pathways", mostly within LTRs, that perforate the SC lipid bilayers and pass through the interiors of hydrated corneocytes. Theoretical estimates of the localized heating within LTRs predict relatively small temperature rises. The theory of LTR formation is incomplete, with both stochastic and deterministic models under consideration. Moderate voltage (MV) pulses leading to about 5<U(skin)<50 V, are consistent with appendageal activation and electroporation. The largest molecular fluxes occur for HV pulses, for which theory predicts large numbers of straight-through aqueous pathways. Both appendageal and stratum corneum electroporation are different from iontophoresis, which occurs at U(skin)<5 V.