CHARACTERIZATION OF CONVECTIVE SOLVENT FLOW DURING IONTOPHORESIS

During iontophoresis under neutral pH conditions, there is a net conve ctive flow of volume (electroosmosis) from anode to cathode leading to the enhanced transport of dissolved polar (but uncharged) solutes in the same direction. The objective of this study was to address the fol lowing unresolved questions with respect to electroosmotic transport: [1] Whether the efficiency of electroosmotic transport is solute size- dependent and, if so, how severe is this dependence? [2] Is electroosm osis linearly related to current density in the same way that the iont ophoretic flux of charged species appears to be? [3] Are positively ch arged permeants able to influence their own electrotransport across th e skin (by modifying the net charge on the membrane and altering, as a result, the permselectivity) and, if so, why and to what extent? Elec troosmosis was assessed from the iontophoreically driven fluxes of man nitol, sucrose and lactose across hairless mouse skin in vitro. It was found that:- (a) The electroosmotic transport rate of mannitol is sim ilar to that of the disaccharides, sucrose and lactose, when examined under identical conditions. The dependence of electroosmotic flux upon molecular size requires study of solutes having a wider range of MW t han those considered here. (b) Electroosmotic flow from anode-to-catho de increases with applied current density; similarly, convective flow in the opposite direction diminishes with increasing current density. Apparently, there is correlation between the net movement of solvent a nd the total flux of ions across the skin. (c) The permselectivity of skin can be 'neutralized' by driving, iontophoretically, a cationic, l ipophilic peptide (specifically the leutinizing hormone releasing horm one (LHRH) analog, Nafarelin) into the membrane. The apparently tight association of the peptide with the fixed, negatively-charged sites in the skin reduces significantly, in a concentration-dependent fashion, the anode-to-cathode electroosmotic flow across the barrier. Peptide lipophilicity appears to be necessary for this effect to be seen: the parent peptide, LHRH, does not exhibit this phenomenon.