Theranostics 2020; 10(6):2849-2858. doi:10.7150/thno.41566

Research Paper

Localized anesthesia of a specific brain region using ultrasound-responsive barbiturate nanodroplets

Harriet Lea-Banks1,2✉, Meaghan A. O'Reilly1,2, Clement Hamani3,4, Kullervo Hynynen1,2,5

1. Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada
2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
3. Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
4. Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
5. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada

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Citation:
Lea-Banks H, O'Reilly MA, Hamani C, Hynynen K. Localized anesthesia of a specific brain region using ultrasound-responsive barbiturate nanodroplets. Theranostics 2020; 10(6):2849-2858. doi:10.7150/thno.41566. Available from http://www.thno.org/v10p2849.htm

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Abstract

Background: Targeted neuromodulation is a valuable technique for the study and treatment of the brain. Using focused ultrasound to target the local delivery of anesthetics in the brain offers a safe and reproducible option for suppressing neuronal activity.

Objective: To develop a potential new tool for localized neuromodulation through the triggered release of pentobarbital from ultrasound-responsive nanodroplets.

Method: The commercial microbubble contrast agent, Definity, was filled with decafluorobutane gas and loaded with a lipophilic anesthetic drug, before being condensed into liquid-filled nanodroplets of 210 ± 80 nm. Focused ultrasound at 0.58 MHz was found to convert nanodroplets into microbubbles, simultaneously releasing the drug and inducing local anesthesia in the motor cortex of rats (n=8).

Results: Behavioral analysis indicated a 19.1 ± 13% motor deficit on the contralateral side of treated animals, assessed through the cylinder test and gait analysis, illustrating successful local anesthesia, without compromising the blood-brain barrier.

Conclusion: Pentobarbital-loaded decafluorobutane-core Definity-based nanodroplets are a potential agent for ultrasound-triggered and targeted neuromodulation.

Keywords: focused ultrasound, triggered drug delivery, phase-change emulsion