Reverse iontophoresis - Parameters determining electroosmotic flow: I. pH and ionic strength

It has been previously demonstrated that electroosmosis (the convective movement of solvent that occurs through a charged 'pore' in response to the preferential passage of counter-ions when an electric field is applied) can be used in 'reverse iontophoresis', where the imposition of an electric current across the skin is used to extract a substance of interest (e.g., glucose) from within or beneath the tissue to the surface of the body. The goal of the research reported here was to examine parameters which determine electroosmosis, such that the convective flow of solvent across the skin during iontophoresis may be maximized, and the sensitivity and precision of the procedure optimized. Using mannitol as an appropriate marker molecule, therefore, electroosmotic flow during reverse iontophoresis has been examined as a function of the pH and ionic strength of the electrolyte solutions contained within the electrode compartments located on the skin surface. The impact of using a limited set of different current waveforms was also studied. As expected from the permselectivity of the skin, extraction to the cathode was preferred over that to the anode at pH 7.4. Cathodal extraction was enhanced by increasing the pH of the surface electrolyte conversely, electroosmosis to the anode was improved by lowering the pH (due, presumably, to neutralization of the net negative charge on the ion-conducting pathways through the skin). Reducing the electrolyte ionic strength in the electrode chambers (relative to the physiological level present beneath the tissue) enhanced both cathodal (in particular) and anodal extraction; a minimum quantity of electrolyte, however, must be present in order to sustain the necessary electrochemistry of the iontophoretic system. Finally, neither periodic interruption of current flow, nor periodic alternation of electrode polarity (strategies which have been proposed to limit the acute irritation induced by constant current iontophoresis, i.e., allowing the skin an opportunity to 'depolarize') adversely affected the overall efficiency of the extraction process.