title: Investigation of properties of human epidermal membrane under constant conductance alternating current iontophoresis.
abstract: Previous studies in our laboratory have shown that enhanced, constant permeant fluxes across human skin can be achieved by applying an alternating current (AC) to maintain skin electrical conductance at a constant level. Relative to conventional direct current (DC) iontophoresis, for which current is maintained at a constant level, this newly developed constant conductance alternating current (CCAC) method achieves constant fluxes with less inter- and intra-sample variability. The present study focused upon further investigating the permeability properties of human skin during CCAC iontophoresis at a variety of target resistance/conductance values. A three-stage experimental protocol was used with flux measurements determined on 3 consecutive days. Stage I was an AC only protocol (symmetrical AC square-wave signal), stage II was an AC plus DC protocol (AC square-wave with DC offset voltage), and stage III was a repeat of stage I. During this three-stage protocol, the skin electrical resistance was maintained at a constant target value by manually adjusting the applied AC voltage. Radiolabeled mannitol and urea were model permeants in all experiments. Their fluxes were determined and used to characterize the permeability properties of human skin. The results from the present study established that: (i) the CCAC protocol made it possible to reduce HEM electrical resistance to different target levels as low as 0.8 kOmega cm(2) and maintain the specific resistance level throughout the flux experiment, (ii) permeant fluxes are proportional to skin electrical conductance, (iii) under the studied CCAC passive conditions, membrane pore size tends to increase as skin resistance decreases, and (iv) as the membrane breaks down, its pore sizes become larger.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Honggang
authors.initials: H
authors.lastname: Zhu
authors.forename: Kendall D
authors.initials: KD
authors.lastname: Peck
authors.forename: David J
authors.initials: DJ
authors.lastname: Miller
authors.forename: Mark R
authors.initials: MR
authors.lastname: Liddell
authors.forename: Guang
authors.initials: G
authors.lastname: Yan
authors.forename: William I
authors.initials: WI
authors.lastname: Higuchi
authors.forename: S Kevin
authors.initials: SK
authors.lastname: Li
mesh_terms: D000279:Administration, Cutaneous; D017097:Electric Impedance; D004817:Epidermis / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007478:Iontophoresis / Q000379:methods*; D008353:Mannitol / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D012879:Skin Physiological Phenomena / Q000187:drug effects*; D013997:Time Factors; D014508:Urea / Q000493:pharmacokinetics
chemical_list: D008353:Mannitol; D014508:Urea