Iontophoretic transport pathways: Dependence on penetrant physicochemical properties

The objective of this work was to investigate how the preferred iontophoretic transport pathways of a molecule depend on its physicochemical properties. Laser scanning confocal microscopy (LSCM) was used to visualize in hairless mouse skin the distribution of two fluorescent penetrants: calcein, a multiply charged (-4), hydrophilic molecule; and nile red, a lipophilic, neutral compound. Iontophoresis and passive delivery of nile red showed that the percutaneous transport of this compound occurred via (inter- and intracellular) pathways that were clearly distinct from those followed by calcein. Although the distribution of nile red was influenced somewhat by the passage of current relative to the passive control, there was relatively little enhancement of the penetration of this compound into the skin. Calcein, on the other hand, did not passively enter the skin. However, with iontophoresis, greatly enhanced transport, with an important contribution from follicular structures, was observed. Sequential (dual) transport of the two fluorophores illustrated clearly the different pathways followed and reflected the transport and visualization studies of the individual species. It may be concluded, therefore, that the iontophoretic pathways followed across the skin are dictated by the physicochemical properties of the penetrant and by its affinity for the different environments available.