Characterization of convective solvent flow during iontophoresis

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Abstract

During iontophoresis under neutral pH conditions, there is a net convective flow of volume (elec-troosmosis) from anode to cathode leading to the enhanced transport of dissolved polar (but uncharged) solutes in the same direction. The objective of this study was to address the following unresolved questions with respect to electroosmotic transport: [1] Whether the efficiency of electroosmotic transport is solute size-dependent and, if so, how severe is this dependence? [2] Is electroosmosis linearly related to current density in the same way that the iontophoretic flux of charged species appears to be? [3] Are positively charged permeants able to influence their own electrotransport across the skin (by modifying the net charge on the membrane and altering, as a result, the permselectivity) and, if so, why and to what extent? Electroosmosis was assessed from the iontophoreically driven fluxes of mannitol, sucrose and lactose across hairless mouse skin in vitro. It was found that:- (a) The electroosmotic transport rate of mannitol is similar to that of the disaccharides, sucrose and lactose, when examined under identical conditions. The dependence of electroosmotic flux upon molecular size requires study of solutes having a wider range of MW than those considered here, (b) Electroosmotic flow from anode-to-cathode increases with applied current density; similarly, convective flow in the opposite direction diminishes with increasing current density. Apparently, there is correlation between the net movement of solvent and the total flux of ions across the skin, (c) The permselectivity of skin can be ‘neutralized’ by driving, iontophoretically, a cationic, lipophilic peptide (specifically the leutinizing hormone releasing hormone (LHRH) analog, Nafarelin) into the membrane. The apparently tight association of the peptide with the fixed, negatively-charged sites in the skin reduces significantly, in a concentration-dependent fashion, the anode-to-cathode electroosmotic flow across the barrier. Peptide lipophilicity appears to be necessary for this effect to be seen: the parent peptide, LHRH, does not exhibit this phenomenon.

Original languageEnglish
Pages (from-to)929-935
Number of pages7
JournalPharmaceutical Research
Volume11
Issue number7
DOIs
Publication statusPublished - Jul 1994

Keywords

  • convective solvent flow
  • electroosmosis
  • iontophoresis
  • LHRH analogs
  • mannitol
  • Nafarelin
  • transdermal peptide delivery

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