Iontophoresis: electrorepulsion and electroosmosis

Over the last 10-15 years, the electrical enhancement of drug delivery across the skin has undergone intense investigation. During this period, considerable amounts of experimental data have been generated, and the successful enhancement of a diverse array of molecules has been achieved. Indeed, the commercial exploitation of the method can be envisaged within the next few years. Despite this progress, however, the mechanistic understanding of iontophoresis remains a challenging scientific question that is yet to be fully resolved. The routes of permeation under the influence of an applied electrical potential, and the molecular interactions of the transporting drug with these pathways, have resisted unequivocal and unambiguous identification. Equally, the relative contributions of electrorepulsion and electroosmosis to the total iontophoretic flux have proven difficult to quantify, due to the difficulty of designing appropriate experiments. The situation is further complicated by the fact that it has now been established that certain lipophilic cations, in particular, can associate strongly with the skin during their iontophoretic delivery, thereby altering the electrical properties of the membrane, and changing the mechanism of transport. In this short communication, the roles of electrorepulsion and electroosmosis have been reconsidered from a simple theoretical point of view, and experimental approaches by which their relative importance may be estimated have been proposed and subjected to initial evaluation.