Abstract
In this study, we used sonophoresis and iontophoresis to enhance the in vitro delivery of methotrexate through human cadaver skin. Iontophoresis was applied for 60 min at a 0.4 mA/sq·cm current density, while low-frequency sonophoresis was applied at a 20 kHz frequency (2 min application, and 6.9 W/sq·cm intensity). The treated skin was characterized by dye binding, transepidermal water loss, skin electrical resistance, and skin temperature measurement. Both sonophoresis and iontophoresis resulted in a significant reduction in skin electrical resistance as well as a marked increase in transepidermal water loss value (p < 0.05). Furthermore, the ultrasonic waves resulted in a significant increase in skin temperature (p < 0.05). In permeation studies, the use of iontophoresis led to a significantly higher drug permeability than the untreated group (n = 4, p < 0.05). The skin became markedly more permeable to methotrexate after the treatment by sonophoresis than by iontophoresis (p < 0.01). A synergistic effect for the combined application of sonophoresis and iontophoresis was also observed. Drug distribution in the skin layers revealed a significantly higher level of methotrexate in the sonicated skin than that in iontophoresis and untreated groups. Iontophoresis and low-frequency sonophoresis were found to enhance the transdermal and intradermal delivery of methotrexate in vitro.