Electroosmotic flow through skin: effect of current duration and poly(ethylene imine)

Abstract

The objective of this work is to investigate the effect of current duration and poly(ethylene imine) on the magnitude and direction of electroosmotic flow (EF), to have a better understanding on the design of iontophoretic transdermal formulation. Such factors as the length of current application time and the addition of poly(ethylene imine)750 K (PEI750K) in the formulation were studied. Experiments were performed in vitro at pH 7.4 using side-by-side diffusion cell and hairless mouse skin. The direction and magnitude of EF were evaluated simultaneously using two neutral marker molecules, acetaminophen (AAP) and caffeine (CAF). The flux data of AAP and CAF were very similar to each other, and demonstrated clearly that EF is playing an important role in their flux. As the current duration increased, not only the passive permeability but also the magnitude of EF increased. The magnitude of EF at 9 h of current application was estimated to be ~1.9 µl/cm2 hr. The flux of AAP and CAF substantially decreased by PEI750K during current application, and it increased after current off, indicating reversion in the direction of EF from the normal anode-to-cathode direction to cathode-to-anode direction. These results suggest that PEI750K molecules seem to adhere to the negatively charged interface of the current conducting pore (CCP), leading to the charge inversion to a positively charged interface. Overall, the results obtained in this work provide a better understanding on the effect of current duration and PEI750K, and the role of EF in transdermal flux during iontophoresis.