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Quantification of pore induction in human epidermal membrane during iontophoresis: the importance of background electrolyte selection.

Abstract：

:It has been shown that significant pore induction (electroporation) occurs in human epidermal membrane (HEM) during iontophoresis even at moderate applied voltages (1-10 V). Recent efforts in our laboratory have been aimed at quantifying HEM electroporation by examining the proportionality between flux enhancement due to electroporation and electrical conductance changes during iontophoresis. The specific purpose of the present study was to test the hypothesis that by matching the background electrolyte ion sizes with the permeant ion sizes, the flux enhancement due to electroporation can be quantified by the change in HEM electrical conductance. In this study, radiolabeled tetraethylammonium (TEA(+)), methylammonium (MA(+)), and mannitol were the permeants. Potassium chloride (KCl), tetraethylammonium bromide (TEAB), tetraethylammonium pivalate (TEAP), and sodium fluoride (NaF) were the background electrolytes. Iontophoresis experiments were carried out over an applied voltage range of 1 to 3 V. The experimental flux enhancement results were compared with the theoretical predictions from the Nernst-Planck model after corrections were made: (a) for HEM pore induction during iontophoresis based on electrical conductance changes and (b) for electroosmosis employing mannitol as the neutral probe permeant. In experiments where the ion sizes of the background electrolyte and permeant were closely matched (e.g., TEA(+) as the permeant and TEAP as the background electrolyte), there was excellent agreement between experimental results and theoretical predictions of the modified Nernst-Planck model, with only modest data scatter. When the electrolyte and permeant sizes were quite different (e.g., TEA(+)/KCl and MA(+)/TEAP), the experimental flux data were inconsistent with model predictions and there were large variations in the experimental results. The results of the present study illustrate that permeant flux enhancement can be predicted by the modified Nernst-Planck model even during moderate voltage iontophoresis when electroporation is operative.

journal_name

J Pharm Sci

journal_title

Journal of pharmaceutical sciences

authors

Zhu H,Peck KD,Li SK,Ghanem AH,Higuchi WI

doi

10.1002/jps.1044

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

932-42

issue

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)30776-6

journal_volume

pub_type

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Quantification of pore induction in human epidermal membrane during iontophoresis: the importance of background electrolyte selection.