Optimization of Ultrasound-Mediated Drug Delivery for Treatment of Onychomycosis

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  • 1 The George Washington University Department of Biomedical Engineering
  • | 2 The George Washington University Department of Podiatry
  • | 3 The George Washington University The Department of Biomedical Engineering
  • | 4 The George Washington University The Department of Biomedical Engineering

Background: Onychomycosis is a fungal nail disorder that does not have a successful cure due to the poor permeability of topical anti-fungal drugs through the nail. This study utilizes ultrasound to increase the permeability of the nail to the topical drugs currently used in clinic. The first aim of this study was to optimize ultrasonic parameters within the temperature increase limits set by the American Institute of Ultrasound in Medicine (AIUM) and the British Medical Ultrasound Society (BMUS). The second aim of the study was to evaluate the optimized parameters for a cause of action of either cavitation (the creation of micrometer pores in the nail barrier) or acoustic streaming (a steady fluid motion which may help push the drug through the nail).

Methods: Porcine and human nails are used in the five studies. PZFlex Modeling Software is used to model the temperature increase in the toe as a result of ultrasonic application and these results were used to develop the three parameters tested throughout the rest of the studies. The three parameters tested were 1 min of continuous ultrasonic application, 3 min of 50% ultrasonic application and 5 min of 50% ultrasonic application. In order to address the second aim of our research work, these three parameters were tested for the presence of streaming and cavitation.

Results: At the three tested parameters, the most permeation of the nail occurs with 1 min of continuous application of ultrasound to the nail. It was also found that there was limited cavitation and significant streaming at all three parameters. This suggests that streaming may be the main mechanism-of-action in ultrasound-mediated drug delivery through the nail.

Conclusion: The parameter of 1 min of continuous ultrasonic testing will continue to be employed as the testing is moved to a rabbit model of onychomycosis.

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