Increased penetration of nonelectrolytes into mouse skin during iontophoretic water transport (iontohydrokinesis)

Abstract

Iontophoresis increases penetration of ionic drugs into surface tissues by repulsion of ions at the active electrode. However, we reported increased penetration of idoxuridine by either anode(+) or cathode(-). Although not highly ionized, idoxuridine forms anions in aqueous solution requiring introduction under the cathode(-). We postulated that increased penetration of idoxuridine after anodal(+)-iontophoresis may result from water movement associated with sodium ion transfer. When water is transported into tissue, nonelectrolytes may also be transported. The term iontohydrokinesis was adopted to describe water transport during iontophoresis, and no specific mechanism is implied by this new term. Iontohydrokinesis was studied after cathodal(-)- and anodal(+)-iontophoresis of dilute NaCl solutions containing [3H]-9-beta-D-arabinofuranosyladenine, (Ara-A), [3H]H2O and [3H]thymidine (dThd). Since Ara-A and dThd are nonconductive, any increase in penetration must be due to water transport by iontohydrokinesis. Anodal iontophoresis resulted in the following statistically significant increases in penetration compared to topical application: [3H]H2O, +155%; [3H]dThd, +429% and [3H]Ara-A, +488%. Cathodal(-)-iontophoresis resulted in statistically significant increases in penetration: [3H]H2O, +78% and [3H]dThd, +286%; the penetration of [3H]Ara-A increased +56% but this was not statistically significant. Electrical current does not change skin permeability.