Localized anesthesia of a specific brain region using ultrasound-responsive barbiturate nanodroplets
Localized anesthesia of a specific brain region using ultrasound-responsive barbiturate nanodroplets
复制标题
超声响应型巴比妥酸盐纳米液滴用于特定脑区的局部麻醉
DOI：
10.7150/thno.41566
复制
发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Hynynen, Kullervo
中科院分区：
文献类型：
--
作者：
Lea-Banks, Harriet;O'Reilly, Meaghan A.;Hynynen, Kullervo
背景：靶向神经调节是研究和治疗脑部疾病的一项有价值的技术。利用聚焦超声靶向麻醉药物在大脑的局部传递，为抑制神经元活动提供了一种安全且可重复的选择。目的：通过超声反应纳米微滴触发戊巴比妥释放，开发一种潜在的局部神经调节新工具。方法：将市售微泡造影剂Definity充入十氟丁烷气体，装入亲脂性麻醉药物，然后浓缩成210 +/- 80 nm的充液纳米液滴。发现0.58 MHz聚焦超声可使纳米液滴转化为微泡，同时释放药物并诱导大鼠运动皮质局部麻醉（n=8）。结果：行为分析显示，通过圆柱体试验和步态分析评估，治疗动物对侧有19.1 +/- 13%的运动障碍，说明局部麻醉成功，没有损害血脑屏障。结论：负载戊巴比妥的十氟丁烷核纳米液滴是超声触发和靶向神经调节的潜在药物。
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.