Mechanistic studies of molecular transdermal transport due to skin electroporation

The application of electrical high voltage pulses has been shown to greatly enhance the transdermal transport of water-soluble compounds. The resistance of the skins most important barrier, the stratum corneum, drops within less than 1 mu s by orders of magnitude. This effect is attributed to electroporation, a nonthermic phenomena known to occur in phospholipid double layers. The striking difference between the stratum corneum lipid layers and the usually investigated phospholipid systems is the phase transition temperature. While Lipid layers used for electroporation experiments are in liquid crystal phase above the phase transition temperature, the stratum corneum lipids (phase transition at approximate to 70 degrees C) form a rigid quasi-crystalline membrane at room temperature. After the electrical stimulus a recovery of the passive flux was found making high voltage pulsing a suitable tool for controlling transdermal drug delivery. By ordinary light microscopy no dramatic changes in skin structure were found supporting the thesis of electroporation. However the microstructure shows clearly persistent structural changes. Recently the involvement of Joule heating due to the electric stimulus was shown as an important factor for skin permeabilization and molecular transport. (C) 1999 Published by Elsevier Science BN.