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.
Highlights
Transdermal drug delivery offers several advantages, such as patient compliance, enhanced bioavailability, and avoidance of first-pass hepatic metabolism [1,2]
Topical or transdermal drug delivery is limited by the skin barrier function—the uppermost lipophilic layer of stratum corneum, which is selectively permeable to certain chemicals [3,4]
Transdermal drug delivery could be enhanced by optimizing the drug formulations or disrupting the integrity of the skin barrier using chemical penetration enhancers or physical methods, such as microneedles, laser, sonophoresis, and iontophoresis (ITP) [9,10,11,12]
Summary
Transdermal drug delivery offers several advantages, such as patient compliance, enhanced bioavailability, and avoidance of first-pass hepatic metabolism [1,2]. These advantages can be achieved only if therapeutically desired blood levels of drugs are obtained. Topical or transdermal drug delivery is limited by the skin barrier function—the uppermost lipophilic layer of stratum corneum, which is selectively permeable to certain chemicals [3,4]. Transdermal drug delivery could be enhanced by optimizing the drug formulations or disrupting the integrity of the skin barrier using chemical penetration enhancers or physical methods, such as microneedles, laser, sonophoresis, and iontophoresis (ITP) [9,10,11,12]
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