Ultrasound-Enhanced Drug Delivery for Treatment of Onychomycosis

NewsBot · Dec 31, 2017

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Ultrasound-Enhanced Drug Delivery for Treatment of Onychomycosis.
Kline-Schoder A, Le Z, Zderic V.
J Ultrasound Med. 2017 Dec 30. doi: 10.1002/jum.14526.

OBJECTIVES:
The aim of our study was to determine the effectiveness of using ultrasound (US) to increase the permeability of the nail, with the goal of improving outcomes in the treatment of onychomycosis.

METHODS:
Porcine nails were used because of their similarity to human nails. A hydrophilic blue dye was used as a drug-mimicking compound. Two sets of experiments were performed: luminosity experiments to assess the dye levels inside the nail after US and sham treatments and diffusion cell experiments for determination of changes in nail permeability due to US application. In both sets of experiments, planar US transducers were used to sonicate the nails at frequencies of 400, 600, and 800 kHz and 1 MHz, an intensity of 1 W/cm2 , and a duration of 5 min in a continuous mode. Modeling studies were also performed to assess the safety of US application to the human toe for later clinical studies.

RESULTS:
In the luminosity experiments, application of US at frequencies of 600 and 800 kHz led to statistically significant results (P < .05), with an increase in dye delivery into the nail of up to 95% compared to control values. The diffusion cell results found statistical significance (P < .05) at all applied frequencies, with up to a 70% increase in the nail permeability compared to the control. Safety modeling studies found a maximal temperature increase of 4.4 °C in the bone.

CONCLUSIONS:
Our proposed US method may offer an alternative for improved treatment of onychomycosis. The current maximal temperature increase was found to be at the safety limit, and so pulsing and other alternatives will be investigated to minimize this temperature increase.
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Admin2 · Dec 31, 2017

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NewsBot · Oct 27, 2019

Optimization of Ultrasound-Mediated Drug Delivery for Treatment of Onychomycosis.
Alina Kline-Schoder,Zung Le, Liam Sweeney, and Vesna Zderic
Journal of the American Podiatric Medical Association In-Press.

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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