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

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.