CHARACTERIZATION OF THE TRANSPORT PATHWAYS INDUCED DURING LOW TO MODERATE VOLTAGE IONTOPHORESIS IN HUMAN EPIDERMAL MEMBRANE

This report describes the results of iontophoresis experiments involvi ng the transport of polar nonelectrolytes across human epidermal membr ane (HEM) at a moderate applied voltage of 2.0 V and where the data ar e interpreted via a convective transport model and hindered transport theory. A principal finding is that although HEM iontophoresis at 2.0 V resulted in a large increase in HEM porosity, the pore radii of the newly induced pores in HEM as calculated from the iontophoresis data u sing the hindered transport theory were found to be in the range of 6- 12 Angstrom. This supports the view that electroporation at these mode st applied voltages results in pores with sizes the same order of magn itude but somewhat smaller than those estimated for the preexisting po res in HEM prior to electroporation. This outcome is also important fr om a practical standpoint, as flux enhancement for large molecules (su ch as oligonucleotides and polypeptides) arising from electroporation under these conditions would be expected to be significantly less than if the resulting pore sizes were much greater. Providing a ''prepulse '' of 4.0, 8.0, and 15 V prior to the 2.0 V iontophoresis generally ga ve greater increases in HEM conductance (and, therefore, in porosity) but did not significantly change the deduced effective pore radii (aro und 5-9 Angstrom). The alteration during and the recovery of HEM after iontophoresis was also investigated. The recovery behavior was found to be dependent upon both the duration of the applied voltage and the magnitude of its effects: the recovery for a HEM sample that experienc ed a large increase in electrical conductance during iontophoresis was generally poorer than that for a sample that was more resistant to th e electric field. Incomplete recovery was generally observed in experi ments with long iontophoresis duration (50 min) and with the higher vo ltages (4.0, 8.0 V, and 15 V). In these cases, the barrier properties of HEM were more greatly altered as indicated by larger increases in t he electrical conductance and passive permeability of HEM after iontop horesis.