Iontophoresis: Applications in drug delivery and noninvasive monitoring

The term iontophoresis typically refers to the transfer of charged substances through a biological membrane under the influence of an electric field (1). This technique is far from new, Leduc having shown nearly 100 years ago that the technique could be used to deliver active drugs across mammalian skin in vivo (2,3). Since then, iontophoresis has been variously used to administer pilocarpine in the diagnosis of cystic fibrosis, to treat hyperhidrosis of palms and soles (tap water iontophoresis), to induce local anaesthesia in the skin and in the external ear canal, to aid penetration of fluoride ions in dentistry, and so on (2-4). Yet it was only 20 years ago, following the initial success of passive transdermal drug delivery, that iontophoresis received attention as a way to expand the range of drugs that could be administered via the skin (5). At the same time, it was fully appreciated (6) that the permeation of water, neutral and zwitterionic compounds could also be enhanced by iontophoresis, thereby expanding its potential applications. This observation, and the recognition of the skin as a permselective membrane, focused attention on convective solvent flow (electroosmosis) as a second mechanism of electrotransport (7). The advantages of iontophoresis as a controlled and versatile drug administration technique were soon identified for peptides and drugs for the treatment of Parkinson’s disease, migraine, pain, etc. Within the last 10 years, the symmetrical nature of iontophoresis (i.e., that the passage of current across the skin causes ions to move into and out of the membrane at the same time) has led to its application as a noninvasive method of extracting endogenous substances (8). This so-called reverse iontophoresis procedure is exemplified by the Glucowatch Biographer® recently approved by the FDA for glucose monitoring.