Transdermal drug delivery using a specialized cavitation seed for ultrasound

The sonophoresis, which utilizes ultrasound for transdermal drug delivery (TDD), can improve the efficiency of drug delivery for a variety of drugs predominantly due to cavitation effect. In order to increase the efficacy of sonophoresis, we propose an alternative cavitation seed specialized for sonophoresis, which can be concentrated on the skin surface by gravity adapting perfluorohexane as core. Methods: In vitro and in vivo experiments were conducted to assess the effect of the specialized cavitation seed. High-performance liquid chromatography (HPLC) was used for in vitro experiments on porcine skin with ferulic acid, and an optical imaging system was used for in vivo experiments on the rat model with fluorescein isothiocyanate-dextran (FD, 150 kDa), respectively. Results: The amount of ferulic acid delivered by sonophoresis with the proposed cavitation seed was approximately 1700 times greater than the amount delivered by diffusion. FD could be delivered to a depth of $500~\mu \text{m}$ under the skin, and the average total flux in the region of interest was increased 6.4-fold for the group using sonophoresis with the cavitation seed compared to the group using diffusion. Conclusion: Conclusively, sonophoresis with the proposed cavitation seed demonstrated the significant improvement in TDD and the possibility of macromolecule delivery into the skin. Significance: This approach has potential to be a main TDD method for variety of applications including medicine and cosmetics.