ELECTROPERTURBATION OF THE HUMAN SKIN BARRIER IN-VITRO .2. EFFECTS ONSTRATUM-CORNEUM LIPID ORDERING AND ULTRASTRUCTURE

In transdermal iontophoresis, drugs can be driven across the skin by e lectrorepulsion, but their transport can also be enhanced by electrica l perturbation of the skin barrier. Our objective was to study perturb ing effects of electrical current on human stratum corneum lipid fine structure combining techniques including freeze-fracture electron micr oscopy. Human stratum corneum was subjected to pulsed constant current s, varying from 0.013-13 mA.cm(-2). The voltage across the stratum cor neum was high-frequency-sampled and s.c. impedance values derived from it. Upon termination of the current, skin samples were rapidly frozen and processed for freeze-fracture electron microscopy or subjected to X-ray diffraction analysis. Initially a rapid decrease of the resista nce and, overall, a rapid increase of the capacitances was observed; g enerally, these effects became more pronounced with increasing current density. Wide- and small-angle X-ray diffractograms of human stratum corneum exposed for 1 h to the highest current indicated a disordering of both the lateral packing arrangement and long-range lamellar stack ing of the intercellular lipids of stratum corneum. Furthermore, an in crease in the stratum corneum hydration level as a result of electrica l current application was observed. On electron micrographs of freeze- fracture replicas of human stratum corneum, exposed for 1 h to current densities between 0.013 and 13 mA.cm(-2), perturbations of the interc ellular lipid structure were observed in accordance with the results o f X-ray diffraction; these perturbations aggravated with increasing cu rrent density. Together, the data suggest that both the lateral and th e longitudinal disordering of the intercellular lipids observed with X -ray diffraction may be responsible for the appearance of perturbed st ructures observed with freeze-fracture electron microscopy. The lipid disordering may be due to polarization of the lipid head groups induce d by the electrical field, followed by mutual repulsion. (C) Wiley-Lis s, Inc.