Discovery of transdermal penetration enhancers by high-throughput screening

Nat Biotechnol. 2004 Feb;22(2):192-7. doi: 10.1038/nbt928. Epub 2004 Jan 4.


Although transdermal drug delivery is more attractive than injection, it has not been applied to macromolecules because of low skin permeability. Here we describe particular mixtures of penetration enhancers that increase skin permeability to macromolecules (approximately 1-10 kDa) by up to approximately 100-fold without inducing skin irritation. The discovery of these mixtures was enabled by an experimental tool, in vitro skin impedance guided high-throughput (INSIGHT) screening, which is >100-fold more efficient than current tools. In vitro experiments demonstrated that the mixtures delivered macromolecular drugs, including heparin, leutinizing hormone releasing hormone (LHRH) and oligonucleotides, across the skin. In vivo experiments on hairless rats with leuprolide acetate confirmed the potency and safety of one such mixture, sodium laureth sulfate (SLA) and phenyl piperazine (PP). These studies show the feasibility of using penetration enhancers for systemic delivery of macromolecules from a transdermal patch.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous*
  • Animals
  • Drug Delivery Systems / methods*
  • Drug Evaluation / methods
  • Drug Synergism*
  • Feasibility Studies
  • Humans
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Vehicles / administration & dosage*
  • Pharmaceutical Vehicles / pharmacokinetics*
  • Rats
  • Skin / drug effects
  • Skin / metabolism*
  • Skin Absorption / drug effects
  • Skin Absorption / physiology


  • Pharmaceutical Preparations
  • Pharmaceutical Vehicles