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

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外文摘要：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 pM 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.

外文关键词：

Poly(amino acid)nanogelControlled drug deliveryInhibition of ferroptosisNeuroprotectionCerebral ischemia injury therapy

作者：

Yunhan Zhang、Zhulin Zou、Shuang Liu、Fangfang Chen、Minglu Li、Haoyang Zou、Haiyan Liu、Jianxun Ding

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作者单位：

Key Laboratory of Pathobiology Ministry of Education,Department of Anatomy,College of Basic Medical Sciences,Jilin University,Changchun 130061,China

Department of Gastrointestinal,Colorectal,and Anal Surgery,China-Japan Union Hospital of Jilin University,Changchun 130033,China

Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaYouth Talents Promotion Project of Jilin ProvinceScience and Technology Development Program of Jilin ProvinceResearch Cooperation Platform Project of Sino-Japanese Friendship Hospital of Jilin University and Basic Medical School of Jilin

项目编号：

U23A2059152203201521731498197117420201920210101114JCKYXZ2022JC04

出版年：

2024

DOI：

10.1016/j.ajps.2024.100886

亚洲药物制剂科学(英文版)

沈阳药科大学

亚洲药物制剂科学(英文版)

ISSN：1818-0876

年,卷(期)：2024.19(2)