Journal of Pharmaceutical Sciences
Characterization of the Permselective Properties of Excised Human Skin During Iontophoresis

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Abstract

The iontophoretic and passive transport of [3H]mannitol, 22Na+, 36CI, 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. For molecules which have a lower relative ability to be transported across the skin (e.g., Ca++ relative to Cl), the ions present in the extracellular fluid (e.g., Cl) can carry a greater percentage of the total current, thus lowering the overall transport efficiency of an ion with a lower relative mobility.

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