Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury  

作　　者：Yunhan Zhang Zhulin Zou Shuang Liu Fangfang Chen Minglu Li Haoyang Zou Haiyan Liu Jianxun Ding 

机构地区：[1]Key Laboratory of Pathobiology Ministry of Education,Department of Anatomy,College of Basic Medical Sciences,Jilin University,Changchun 130061,China [2]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China [3]Department of Gastrointestinal,Colorectal,and Anal Surgery,China-Japan Union Hospital of Jilin University,Changchun 130033,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第2期89-101,共13页亚洲药物制剂科学（英文）

基　　金：supported by the National Natural Science Foundation of China(Grant No.U23A20591,52203201,52173149,and 81971174);the Youth Talents Promotion Project of Jilin Province(Grant No.202019);the Science and Technology Development Program of Jilin Province(Grant No.20210101114JC);Research Cooperation Platform Project of Sino-Japanese Friendship Hospital of Jilin University and Basic Medical School of Jilin University(Grant No.KYXZ2022JC04).

摘　　要：Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

关 键 词：Poly(amino acid)nanogel Controlled drug delivery Inhibition of ferroptosis NEUROPROTECTION Cerebral ischenia injury therapy 

分 类 号：R943[医药卫生—药剂学]