Electroporation of Mammalian Skin: A Mechanism to Enhance Transdermal Drug Delivery

Mammalian skin owes its remarkable barrier function to its outermost and dead layer, the stratum corneum. Transdermal transport through this region occurs predominantly through intercellular lipids, organized largely in bilayers. Electroporation is the creation of aqueous pores in lipid bilayers by the application of a short (microseconds to milliseconds) electric pulse. Our measurements suggest that electroporation occurs in the intercellular lipid bilayers of the stratum corneum by a mechanism involving transient structural changes. Flux increases up to 4 orders of magnitude were observed with human skin in vitro for three polar molecules having charges between -1 and -4 and molecular weights up to slightly more than 1000. Similar flux increases were observed in vivo with animal skin. These results may have significance for drug delivery and other medical applications.