Scanning electrochemical microscopy of iontophoretic transport in hairless mouse skin. Analysis of the relative contributions of diffusion, migration, and electroosmosis to transport in hair follicles.

Scanning electrochemical microscopy (SECM) is used to measure spatially localized diffusive and iontophoretic transport rates in hairless mouse skin. Molecular fluxes within individual hair follicles are quantified by measuring the rate at which redox-active probe molecules emerge from the follicle. The influence of an applied current on the flux of an anion (ascorbate), a cation (ferrocenylmethyltrimethylammonium), and a neutral molecule (acetaminophen) is used to determine the contributions of diffusion, migration, and electroosmosis to iontophoretic transport. The direction of electroosmotic transport is consistent with hair follicles possessing a net negative charge at neutral pH. Electroosmosis results in a modest increase in the transport rate of the neutral molecule (a factor of approximately 2.4x at an iontophoretic current density of 0.1 mA/cm(2)). Larger enhancements in the flux of the electrically charged species are associated with migration. The electroosmotic flow velocity within hair follicles is established to be 0.5 (+/-0.1) microm/s at 0.1 mA/cm(2), independent of the electrical charge of permeant. The net volume flow rate across skin resulting from electroosmosis in hair follicles is estimated to be 0.3 microL/cm(2)h. The results suggest that hair follicles are a significant pathway for electroosmotic solution flow during iontophoresis. The radius of the hair follicle openings in hairless mouse skin is measured to be 21 +/- 5 microm.