Analysis of enhanced transdermal transport by skin electroporation

Abstract

The transport of charged molecules across human skin can be dramatically enhanced by application of high-strength, pulsed electric fields. This phenomenon is theoretically characterized here in terms of the electroporation of lipid bilayers within the stratum corneum above the transbilayer voltage for which electropores have been observed in single bilayer membranes. Accounting for the size, shape and charge of the transporting molecules, predictions of transdermal molecular flux are made in two electric field conditions. At small field strengths (transdermal voltage ⪡ 100 V), representative of standard skin iontophoresis, charged molecules are modeled as transporting through the pre-existing shunt routes of the skin. At electric field strengths sufficiently large (transdermal voltage > 100 V) to electroporate lipid bilayers, a transcorneocyte pathway is accessible to charged molecules, with transbilayer transport occurring through electropores within the lipid bilayers. Experimental data of transdermal molecular flux compared favorably with the respective theoretical predictions in the small and large electric field strength limits. Predictions of the skin's electrical resistance are also found to be consistent with experimental data at small and large electric field strengths. In both limits, electrophoretic transport is shown to be predominantly convective (i.e., dominated by electric-field drift); however, a unique form of transport enhancement involving convective dispersion may be significant during skin electroporation.