Characterization of the permselective properties of excised human skin during iontophoresis.
The iontophoretic and passive transport of [3H]mannitol, 22Na+, 36Cl-, and 45Ca++ across excised human cadaver skin was studied using diffusion cells. The anode (+) was placed in the side of the diffusion cell facing the epidermis and the cathode (-) was placed in the side facing the dermis, and current densities at 0, 0.078, 0.16, and 0.23 mA.cm-2 were investigated. The results showed that mannitol and Na+ were transported preferentially by anodal (+) iontophoresis, Cl- was transported by cathodal (-) iontophoresis, and all respective fluxes were approximately proportional to the applied current density. When the skin was present as a membrane barrier between the two diffusion cell chambers the voltage induced flux of Na+ was found to be higher than its free solution value, and that of Cl- was lower. Taken together these results suggest that the skin is a permselective membrane and exists with an "apparent" net negative charge at the free solution pH of 7.4. During iontophoresis this permselectivity leads to current-induced volume flow, which provides a primary mechanism for the transport for a polar uncharged molecule such as mannitol. When Ca++ is substituted for Na+ on the side of the diffusion cell facing the epidermis, the Cl- flux from the dermal side is enhanced with a portion of the remaining charge being carried by Ca++. The mannitol flux from the epidermal side was decreased under these conditions. This implies that Ca++ alters the anion/cation flux ratio in the excised tissue, possibly by binding to fixed negative charges in the membrane, with the result that the volume flow is decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001692:Biological Transport; D002712:Chlorides / Q000493:pharmacokinetics; D004058:Diffusion; D005260:Female; D006801:Humans; D007478:Iontophoresis; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009995:Osmosis; D012869:Skin Absorption; D012964:Sodium / Q000493:pharmacokinetics
D002712:Chlorides; D008353:Mannitol; D012964:Sodium