Optimization of bipolar iontophoresis parameters for the skin penetration of a negatively charged hydrophilic cosmetic active.

Iontophoresis uses low electrical currents to enhance the transdermal delivery of ionic drugs through a combined effect of electromigration (EM) and electroosmosis (EO). This study investigated the cutaneous penetration of an anti-ageing agent, ascorbyl glucoside (AA2G), loaded in a simple buffered aqueous gel, using cathodal direct current iontophoresis. The iontophoresis device consisted of two electrodes applied side by side to the skin surface. For gels prepared at pH 2.6, AA2G was only slightly ionized, and despite the positive skin surface charge, the application of an electric current of 0.1 mA/cm² had no impact on AA2G skin penetration compared to passive diffusion. However, at pH 6, where AA2G is highly ionized and the skin explant is negatively charged, the similar contributions of electroosmosis and electromigration led to a significantly higher total amount of AA2G in the skin (Qtot ∼1.697 ± 0.178 µg/cm²) than with passive diffusion (Qtot ∼0.258 ± 0.105 µg/cm²). This corresponded to a 9.6-fold improvement in AA2G penetration into its target skin layers (dermis and epidermis). At higher current densities (above 0.2 mA/cm²), EM of AA2G increased further, but skin polarization and the increased transport of mobile cations (endogenous and from the buffered gel) resulted in greater electroosmotic flux, thus reducing AA2G overall cutaneous penetration. The results also showed that depositing the AA2G formulation under both electrodes, with no formulation in between, promoted AA2G skin penetration, whatever the current intensity. Cathodic iontophoresis is suitable for the transdermal delivery of AA2G, a small, hydrophilic and negatively charged molecule, despite the skin permselectivity to cations.