Rapid skin permeabilization by the simultaneous application of dual-frequency, high-intensity ultrasound
Author(s)Polat, Baris E.; Mendenhall, Jonathan David; Maa, Ruby C.; Jones, Brianna; Langer, Robert; Blankschtein, Daniel; Schoellhammer, Carl; Hart, Douglas; ... Show more Show less
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Low-frequency ultrasound has been studied extensively due to its ability to enhance skin permeability. In spite of this effort, improvements in enhancing the efficacy of transdermal ultrasound treatments have been limited. Currently, when greater skin permeability is desired at a given frequency, one is limited to increasing the intensity or the duration of the ultrasound treatment, which carries the risk of thermal side effects. Therefore, the ability to increase skin permeability without increasing ultrasound intensity or treatment time would represent a significant and desirable outcome. Here, we hypothesize that the simultaneous application of two distinct ultrasound frequencies, in the range of 20 kHz to 3 MHz, can enhance the efficacy of ultrasound exposure. Aluminum foil pitting experiments showed a significant increase in cavitational activity when two frequencies were applied instead of just one low frequency. Additionally, in vitro tests with porcine skin indicated that the permeability and resulting formation of localized transport regions are greatly enhanced when two frequencies (low and high) are used simultaneously. These results were corroborated with glucose (180 Da) and inulin (5000 Da) transdermal flux experiments, which showed greater permeant delivery both into and through the dual-frequency pre-treated skin.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Massachusetts Institute of Technology. Department of Mechanical Engineering
Journal of Controlled Release
Schoellhammer, Carl M., Baris E. Polat, Jonathan Mendenhall, Ruby Maa, Brianna Jones, Douglas P. Hart, Robert Langer, and Daniel Blankschtein. “Rapid Skin Permeabilization by the Simultaneous Application of Dual-Frequency, High-Intensity Ultrasound.” Journal of Controlled Release 163, no. 2 (October 2012): 154–160.
Author's final manuscript