Quantitative description of the effect of molecular size upon electroosmotic flux enhancement during iontophoresis for a synthetic membrane and human epidermal membrane

This study focused upon quantitatively determining the influence of permeant molecular size upon flux enhancement which results from electroosmosis. The first phase of the study involved validation of a fundamental model describing the molecular size dependence of flux enhancement which results from convective solvent flow. This was accomplished using a model synthetic membrane (stack of 50 Nuclepore membranes) and four model permeants with a molecular weight range of 60-504 (urea, mannitol, sucrose, and raffinose). The steady-state flux of each permeant was determined under passive conditions and applied voltages of 125, 250, 500, and 1000 mV using side-by-side diffusion cells and a four-electrode potentiostat system. On the basis of the permeability enhancement for each permeant at each applied voltage (relative to the passive permeability) it was possible to calculate the effective solvent flow velocity from each permeant at each field strength. An important finding was that the flux enhancement due to electroosmosis was strongly molecular weight dependent (i.e., the flux enhancement ratio was around 4 times greater for raffinose than for urea, with mannitol and sucrose yielding intermediate values), while the calculated effective flow velocity at each voltage was independent of the molecular weight of the permeant. This coupled with a linear correlation between flow velocity and applied voltage served to establish the validity of the method and model. The second phase of the study was an extension of the model to human epidermal membrane (HEM). These experiments involved simultaneously measuring the fluxes of [C-14]urea and [H-3]sucrose across HEM samples under passive, 250 mV, and 500 mV conditions. Similar to the Nuclepore system, the observed flux enhancement ratios with HEM were approximately 3 times greater for sucrose than for urea. A detailed analysis of the HEM data showed semiquantitative agreement between predictions of the model and experimental results.