Transdermal Drug Delivery Aided by an Ultrasound Contrast Agent: An In Vitro Experimental Study

Donghee Park1, Jinhee Yoon1, Jingam Park1, Byungjo Jung1, Hyunjin Park2, Jongbum Seo*, 1
1 Department of Biomedical Engineering, Yonsei University, 234 Maeji, Heungup, Wonju, Kangwon, 220-710, S. Korea
2 Department of Biomedical Engineering, Gachon University of Medicine and Science, Incheon, Korea, 534-2 Yeonsu, Incheon, 406-799, S. Korea

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© Park et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Biomedical Engineering, Yonsei University, S. Korea; Tel: +82-(0)33-760-2961; Fax: +82-(0)33-765-5483; E-mail:


Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity® in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD).

Keywords: Transdermal drug delivery, ultrasound contrast agent, cavitation, sonophoresis, non-invasive drug delivery, optical clearing agent..