Sites of iontophoretic current flow into the skin: Identification and characterization with the vibrating probe electrode

The routes taken by charged substances (e.g., peptides) through the skin during iontophoretic drug delivery are not well characterized. We have used a vibrating probe electrode to reproducibly identify and vectorize site-specific (spatial resolution = 20 μm) ionic flows as they were occurring in hairless mouse skin clamped at clinically relevant current densities. These iontophoretic currents were primarily appendageal, and certain appendages (e.g., small hairs) appeared to carry most of the current. This finding may have important ramifications with respect to irritation, allergic reaction, and electrical current damage in iontophoretic drug delivery. The size and direction of the current vectors could change under certain conditions (e.g., in an unbuffered preparation, where pH changes occurred during the experiment). The vibrating probe can operate in (and is not adversely affected by) the ranges of pH, tonicity, and current required for the study of iontophoretic currents.