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)