Sk. Li et al., IONTOPHORETIC TRANSPORT ACROSS A SYNTHETIC MEMBRANE AND HUMAN EPIDERMAL MEMBRANE - A STUDY OF THE EFFECTS OF PERMEANT CHARGE, Journal of pharmaceutical sciences, 86(6), 1997, pp. 680-689
The effects of permeant charge (z) on iontophoretic-enhanced transport
were investigated with synthetic Nuclepore membranes and with human e
pidermal membranes using a four-electrode potentiostat with side-by-si
de diffusion cells. The modified Nernst-Planck model (Nernst-Planck th
eory with an additional transport term to correct for the effect of th
e convective solvent flow due to electroosmosis) was first examined in
a Nuclepore membrane system with model permeants calcein (z = -4), sa
licylate (z = -1), and a series of polystyrene sulfonates (from monome
r to molecular weight of similar to 8000 with a z range of -1 to simil
ar to -40). The flux enhancement (E) for each permeant was determined
at 470 mV. Mannitol (a neutral molecule) was used as a probe to determ
ine a correction for convective solvent flow under the same applied vo
ltage conditions. Good agreement between the experimental results and
the predictions from the modified Nernst-Planck model was found for ca
lcein, salicylate, and polystyrene sulfonates up to molecular weight o
f similar to 1800 (z similar to -8). The flux enhancements for the hig
her molecular weight polystyrene sulfonates with greater z values were
more than a factor of three lower than theoretical predictions; the e
lectrophoretic effect and counterion binding to the permeants are prop
osed as possible explanations for these discrepancies between experime
nt and the modified Nernst-Planck theory. In the studies with human ep
idermal membranes, iontophoretic flux enhancements for calcein, salicy
late, and taurocholate were determined at 250 and/or 470 mV. The flux
enhancements were generally consistent with the results calculated fro
m the modified Nernst-Planck model.