Effect of combination of low-frequency sonophoresis or electroporation with iontophoresis on the mannitol flux or electroosmosis through excised skin

Abstract

In vitro permeation studies of mannitol were conducted across excised hairless mouse skin to determine and compare the enhancing effect of electroporation (EP) or sonophoresis (SP) combined with iontophoresis (IP) on the electroosmotic flow, and to analyze the enhancement mechanism of these combined methods. Mannitol flux was utilized as an index for the electroosmotic flow due to its low molecular weight and no electrorepulsion effect. The combination of SP and IP (SP/IP) resulted in an apparent increase of electroosmotic flow (no effect was sometimes observed by SP/IP), while that of EP and IP (EP/IP) had no synergistic enhancing effect on the electroosmosis. Next, the combined effect of tape-stripping (TS) and IP (TS/IP) was examined in a similar manner to clarify the difference between the SP/IP and EP/IP effects on electroosmosis. When the TS number increased from 0 to 3, the electroosmotic flow increased with the TS number. However, no further increase was observed when the TS number became more than 3, and the flow started to decrease when the TS number became 5. The electric charge of the skin surface was then measured after SP or TS application. When SP was applied, the skin surface charge became much more negative and the electroosmotic flow by SP/IP was markedly increased. Thus, an increase in the electroosmotic flow across the skin during IP application can be obtained not by EP and TS, but by SP. The combined use of SP and IP is a promising means for the enhanced skin delivery of non-electrolyte drugs.