ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy  

作　　者：Zheng Zhou Keying Li Yongchao Chu Chao Li Tongyu Zhang Peixin Liu Tao Sun Chen Jiang 

机构地区：[1]Department of Pharmaceutics,School of Pharmacy,Fudan University、Key Laboratory of Smart Drug Delivery,Ministry of Education、State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Shanghai 201203,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第3期1246-1261,共16页药学学报（英文版）

基　　金：support from the National Natural Science Foundation of China (81872808,82121002);Key Projects of Shanghai Science Founation (19JC1410800,China);Shanghai Municipal Science and Technology Major Project(2018SHZDZX01,China);ZJLab

摘　　要：As a neurological disorder in the brain,epilepsy is not only associated with abnormal synchronized discharging of neurons,but also inseparable from non-neuronal elements in the altered microenvironment.Anti-epileptic drugs(AEDs)merely focusing on neuronal circuits frequently turn out deficient,which is necessitating comprehensive strategies of medications to cover over-exciting neurons,activated glial cells,oxidative stress and chronic inflammation synchronously.Therefore,we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation.In brief,reactive oxygen species(ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol(PEG)to form amphiphilic copolymers.Additionally,dehydroascorbic acid(DHAA),an analogue of glucose,was applied to target glucose transporter 1(GLUT1)and facilitate micelle penetration across the blood‒brain barrier(BBB).A classic hydrophobic AED,lamotrigine(LTG),was encapsulated in the micelles via self-assembly.When administrated and transferred across the BBB,ROS-scavenging polymers were expected to integrate anti-oxidation,anti-inflammation and neuro-electric modulation into one strategy.Moreover,micelles would alter LTG distribution in vivo with improved efficacy.Overall,the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.

关 键 词：EPILEPSY Polymeric micelle Reactive oxygen species Inflammation GLIOSIS NEUROPROTECTION 

分 类 号：R749.1[医药卫生—神经病学与精神病学]