Iontophoresis of monomeric insulin analogues in vitro: Effects of insulin charge and skin pretreatment

Lotte Langkjær, Jens Brange, Gerold M. Grodsky, Richard H. Guy

Research output: Contribution to journalArticlepeer-review

10 Citations (SciVal)

Abstract

The aim of this study was to investigate the influence of association state and net charge of human insulin analogues on the rate of iontophoretic transport across hairless mouse skin, and the effect of different skin pretreatments on said transport. No insulin flux was observed with anodal delivery probably because of degradation at the Ag/AgCl anode. The flux during cathodal iontophoresis through intact skin was insignificant for human hexameric insulin, and only low and variable fluxes were observed for monomeric insulins. Using stripped skin on the other hand, the fluxes of monomeric insulins with two extra negative charges were 50-100 times higher than that of hexameric human insulin. Introducing three additional charges led to a further 2-3-fold increase in flux. Wiping the skin gently with absolute alcohol prior to iontophoresis resulted in a 1000-fold increase in transdermal transport of insulin relative to that across untreated skin, i.e. to almost the same level as stripping the skin. The alcohol pretreatment reduced the electrical resistance of the skin, presumably by lipid extraction. In conclusion, monomeric insulin analogues with at least two extra negative charges can be iontophoretically delivered across heirless mouse skin, whereas insignificant flux is observed with human, hexameric insulin. Wiping the skin with absolute alcohol prior to iontophoresis gave substantially improved transdermal transport of monomeric insulins resulting in clinically relevant delivery rates for basal treatment.

Original languageEnglish
Pages (from-to)47-56
Number of pages10
JournalJournal of Controlled Release
Volume51
Issue number1
DOIs
Publication statusPublished - 23 Jan 1998

Keywords

  • Insulin
  • Iontophoresis
  • Monomeric insulin analogues
  • Skin pretreatment
  • Transdermal delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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