Heparin alters transdermal transport associated with electroporation

Biochemical and Biophysical Research Communications
J C WeaverM R Prausnitz

Abstract

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.

References

Nov 1, 1995·Biochimica Et Biophysica Acta·U PliquettJ C Weaver
Aug 11, 1995·Science·S MitragotriR Langer
Apr 1, 1993·Journal of Cellular Biochemistry·J C Weaver
Nov 1, 1995·Bio/technology·M R PrausnitzJ C Weaver

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Citations

Jun 6, 2000·Advanced Drug Delivery Reviews·M R Prausnitz
Mar 17, 2004·Advanced Drug Delivery Reviews·Anne-Rose DenetVéronique Préat
Sep 2, 1999·Journal of Controlled Release : Official Journal of the Controlled Release Society·L IlicJ C Weaver
Feb 26, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yoshihiro Tokudome, Kenji Sugibayashi
Aug 26, 1998·Journal of Drug Targeting·V RegnierV Préat
Nov 13, 2014·IEEE Transactions on Bio-medical Engineering·Chunlan JiangJohn Bischof
Jul 21, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·S Narasimha MurthySek Wen Hui
Jun 17, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Nusrat A Motlekar, Bi-Botti C Youan
Sep 27, 2002·Biophysical Journal·Arindam SenSek Wen Hui
Mar 4, 1999·International Journal of Pharmaceutics·A K BangaT K Ghosh
Aug 2, 2012·Toxicology and Industrial Health·Heidi P ChanHoward I Maibach
Sep 20, 2008·International Journal of Pharmaceutics·S S S LankeA K Banga
Jun 27, 2020·Advanced Drug Delivery Reviews·Tao SunSamir Mitragotri
Aug 14, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·B W Barry

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