Heparin alters transdermal transport associated with electroporation

Short, high-voltage (HV; U(skin,max) approximately 100 V) pulses have been shown to increase rates of transdermal transport by several orders of magnitude via a mechanism hypothesized to involve electroporation. We show that heparin, a linear, highly charged macromolecule, significantly alters the molecular transport capacity and lifetime of aqueous pathways across human stratum corneum (SC) created by such pulses. If co-transported during pulsing, heparin molecules can interact with the SC and other molecules, thereby altering ionic and molecular transport. We also observed an increase in post-pulse skin permeability and persistent lower skin resistance. Because most heparin molecules are long enough to span the five to six lipid bilayer membranes that separate corneocytes within the SC, these results can be explained by the hypothesis that heparin molecules were trapped within the skin, holding open pathway segments connecting adjacent corneocytes. These results support the skin electroporation hypothesis and provide the first demonstration of a chemical enhancer effect for transdermal transport by HV pulsing.