38 Citations (SciVal)


'Reverse iontophoresis' involves the imposition of an electrical potential gradient across the skin with the goal of non-invasively extracting molecules of biological interest to the body surface. A number of potential clinical chemistry applications (in particular, the monitoring of blood sugar) have been envisaged. The ultimate objective of the research described in this paper is to optimize the electro-osmotic component of reverse iontophoretic extraction. In vitro experiments, using diffusion cells in which both electrode chambers are situated on the epidermal side of hairless mouse skin, were performed. Current (0.56 mA/cm2) was passed for 2 h via Ag/AgCl electrodes and the electro-osmotic extraction of radiolabeled mannitol from the receptor phase (5 mM mannitol in pH 7.4 HEPES-buffered saline (0.14 M)) was measured as a function of the formulations placed in the anodal and cathodal chambers. Mannitol represented a non-ionizable, non-metabolizable model compound, which has been used extensively in previous electrotransport experiments of this kind. It was found that iontophoresis of divalent ions from the anode chamber (i.e. an anode formulation with CaCl2 or MgCl2 instead of NaCl) increased electro-osmotic flow from beneath the skin surface towards the anode (i.e. modulation of the normal situation in which the skin's permselectivity dictates net electro-osmosis in the opposite direction). Shielding of the net negative charge on the skin is a possible mechanism for this phenomenon, a hypothesis not inconsistent with the ability of certain lipophilic peptides (e.g, the luteinizing hormone releasing hormone analog, Nafarelin) to achieve a similar effect. In the cathode chamber, to which electro-osmosis predominates, ~3-fold levels of enhancement were achieved by formulating the electrode bathing solution with either 2 mM calcein, 50-300 USP U/ml heparin, or 10 mM EDTA. It is postulated that this augmentation of electrotransport involves either binding of endogenous Ca2+ (and hence decreased shielding of the negative charge on the skin), or simply the presence of more negativity in the membrane (or a combination of the two). Overall, the results demonstrate that electro-osmosis can be increased by manipulation of the electrode formulations, and that commonly used pharmaceutical excipients are among those materials which can be used to optimize the transport.

Original languageEnglish
Pages (from-to)29-36
Number of pages8
JournalJournal of Controlled Release
Issue number1
Publication statusPublished - 30 Oct 1996

Bibliographical note

Funding Information:
Financial support was provided by Cygnus, Inc. and by the US National Institutes of Health (HD-27839). We thank our colleagues in the Skin Bioscience Group at UCSF, and Drs. R. Potts and J. Tamada of Cygnus, for helpful discussions and suggestions.


  • Electro-osmosis
  • Iontophoresis
  • Mannitol
  • Non-invasive monitoring
  • Percutaneous absorption
  • Reverse iontophoresis
  • Skin penetration

ASJC Scopus subject areas

  • Pharmaceutical Science


Dive into the research topics of 'Reverse iontophoresis: Parameters determining electro-osmotic flow. II. Electrode chamber formulation'. Together they form a unique fingerprint.

Cite this