title: Macromolecules as novel transdermal transport enhancers for skin electroporation.
abstract: OBJECTIVE
  Macromolecules were investigated as chemical enhancers of transdermal transport by skin electroporation. Although unable to enhance passive or iontophoretic transport, macromolecules are proposed to enhance electroporation-assisted delivery by stabilizing the increased permeability caused by high-voltage pulses.
  
  
  METHODS
  To test this hypothesis, we examined the timescale of transport, the influence of electrical protocol and the influence of macromolecule size, structure, and charge on enhancement of transdermal mannitol transport in vitro by heparin, dextran-sulfate, neutral dextran, and poly-lysine.
  
  
  RESULTS
  Skin electroporation increased transdermal mannitol delivery by approximately two orders of magnitude. The addition of macromolecules further increased transport up to five-fold, in support of the proposed hypothesis. Macromolecules present during pulsing enhanced mannitol transport after pulsing for hours, apparently by a macromolecule-skin interaction. No enhancement was observed during passive diffusion or low-voltage iontophoresis, suggesting that macromolecules interact specifically with transport pathways created at high voltage. Although all macromolecules studied enhanced transport, those with greater charge and size were more effective.
  
  
  CONCLUSIONS
  This study demonstrates that macromolecules can be used as transdermal transport enhancers uniquely suited to skin electroporation.
authors.affiliation: Unité de Pharmacie galénique, Ecole de Pharmacie, Université catholique de Louvain, Brussels, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Vanbever
authors.forename: M R
authors.initials: MR
authors.lastname: Prausnitz
authors.forename: V
authors.initials: V
authors.lastname: Préat
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016264:Dextran Sulfate / Q000494:pharmacology; D018274:Electroporation; D005079:Excipients; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008353:Mannitol / Q000008:administration & dosage / Q000493:pharmacokinetics; D011107:Polylysine / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects*; D013268:Stimulation, Chemical
chemical_list: D005079:Excipients; D011108:Polymers; D011107:Polylysine; D008353:Mannitol; D006493:Heparin; D016264:Dextran Sulfate