Ultrasound combined blood-brain barrier targeting brain delivery of four-in-one molecular aggregates for the enhancement of anesthetic efficacy and toxicity reduction via propofol-etomidate synergistically inhibition GABA receptor  

作　　者：Shuo Zhang Yishu Wang Mingting Zhu Bingyang Liu Wenpu Zhao Shuai Zhang Ji Xia Lei Shi Peng Tang Feiqian Wang Siyuan Zhang Mingxi Wan Daocheng Wu Wei Gao 

机构地区：[1]The Key Laboratory of Biomedical Information Engineering of Ministry of Education,School of Life Science and Technology,Xi’an Jiaotong University,Xi’an,People’s Republic of China [2]Department of Anesthesiology and Center for Brain Science and Center for Translational Medicine,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an,People’s Republic of China

出　　处：《Aggregate》2024年第5期245-264,共20页聚集体（英文）

基　　金：Young Top-notch Talents of“High-level Talents Special Support Program”of Shaanxi Province;National Natural Science Foundation of China,Grant/Award Numbers:81971290,82102074。

摘　　要：To enhance the anesthetic efficacy and reduce toxic side effects,a strategy is proposed involving the utilization of general anesthetics of Propofol(Pro)and Eto-midate(Eto)to synergistic inhibition GABA receptors simultaneously.Four-in-one molecular aggregates were prepared to implement this strategy,which comprised of Pro and Eto with the bridging molecule monoglyceride monooleate(GMO)and sur-factant F127 through intermolecular forces.The blood-brain barrier(BBB)targeted lactoferrin(LF)is affixed to their surface,obtaining thefinal molecular aggregates.By employing lactoferrin enrich aggregates to the BBB,followed by ultrasound combine microbubbles to open the BBB,a remarkable 4.5-fold enhancement in brain drug delivery was achieved.The molecular aggregates group maintained sta-ble parameters of heart rate,diastolic blood pressure,and systolic blood pressure.A notable increase of more than twice therapeutic index(TI)value was observed,implying their higher anesthesia efficiency and reduced toxicity.Electroencephalo-gram(EEG)experiments demonstrate a significant elevation in the proportion of θ waves from 28%to 80%for aggregates,accompanied by a nearlyfivefold reduc-tion in the proportion ofθwaves,meaning a significant improvement in synergistic anesthesia effectiveness(interaction index 0.289)with lower drug dosage.Further-more,mouse immunofluorescence brain slice experiments suggest Pro and Eto enter the GABA receptor simultaneously,resulting in synergistic inhibition of GABA receptors.

关 键 词：blood-brain barrier brain delivery GABA receptor molecular aggregates synergistic anesthetic efficacy 

分 类 号：R744.51[医药卫生—神经病学与精神病学]