Iontophoresis of a model peptide across human skin in vitro: effects of iontophoresis protocol, pH, and ionic strength on peptide flux and skin impedance.
This study deals with effects of electrical (current density, frequency and duty cycle) and chemical (buffer pH and ionic strength) conditions on the flux of the octapeptide, 9-desglycinamide, 8-arginine-vasopressin (DGAVP), through dermatomed human skin. A pulsed constant current was applied during iontophoresis. The anode faced the anatomical surface of the skin samples inside the diffusion cells. The resistive and capacitative components of the equivalent electrical circuit of human skin could be calculated by fitting the voltage response to a bi-exponential equation. The skin resistance prior to iontophoresis varied between 20 and 60 k omega.cm2. During iontophoresis a decrease of skin resistance and an increase of the series capacitances was observed, which were most pronounced during the first hour of iontophoresis; thereafter both quantities gradually levelled off to an apparent steady state value. The reduction of the resistance during iontophoresis increased non-linearly with increasing current density between 0.013-0.64 mA.cm-2. The steady state resistance and capacitances did not vary significantly with frequency and duty cycle of the current pulse. There was no pH dependence of skin resistance at steady state. Between pH 4 and 10, the steady state peptide flux had a bell-shaped pH-dependence with a maximum of 0.17 nmol.cm-2.h-1 at pH 7.4, which is close to the I.E.P. of the peptide. Lowering the ionic strength from 0.15 to 0.015 M NaCl increased the steady state flux at pH 5 and pH 8 by a factor 5 to 0.28 +/- 0.21 and 0.48 +/- 0.37 nmol.cm-2.h-1, respectively. Together these observations suggested that DGAVP is transported predominantly by volume flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Craane-van Hinsberg
W H
WH
Leiden/Amsterdam Center for Drug Research, Division of Pharmaceutical Technology, Gorlaeus Laboratories, The Netherlands.
Bax
L
L
Flinterman
N H
NH
Verhoef
J
J
Junginger
H E
HE
Boddé
H E
HE
D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004058:Diffusion; D017097:Electric Impedance; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007478:Iontophoresis; D009994:Osmolar Concentration; D012867:Skin / Q000378:metabolism*
D001127:Arginine Vasopressin; C015119:argipressin, des-GlyNH2(9)-