Intelligent lesion blood–brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection  

作　　者：Xueqin He Xiaorong Wang Lianyi Yang Zhihang Yang Wenqi Yu Yazhen Wang Rui Liu Meiwan Chen Huile Gao 

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [2]State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Macao 999078,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第4期1987-1999,共13页药学学报（英文版）

基　　金：supported by National Natural Science Foundation of China (81872806, 81961138009);111 Project (B18035, China);the Fundamental of Research Funds for the Central Universities (China);the Open Research Fund of Chengdu University of Traditional Chinese Medicine;the Open Research Fund of Chengdu University of Traditional Chinese Medicine State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China

摘　　要：The treatment of Alzheimer's disease(AD)is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier(BBB)permeability and unsatisfactory intra-brain distribution of drugs.Therefore,we established an ibuprofen and FK506 encapsulated drug co-delivery system(Ibu&FK@RNPs),which can target the receptor of advanced glycation endproducts(RAGE)and response to the high level of reactive oxygen species(ROS)in AD.RAGE is highly and specifically expressed on the lesion neurovascular unit of AD,this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain.Meanwhile,these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS.As a result,the cognition of AD mice was significantly improved and the quantity of Aβplaques was decreased.Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons.Besides,the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1βin the brain.Overall,Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD lesion.Thus it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection.

关 键 词：Receptor for advanced glycation end products ROS-responsive Blood‒brain barrier transcytosis Alzheimer’s disease Drug combination Anti-neuroinflammation NEUROPROTECTION Nano drug delivery system 

分 类 号：R943[医药卫生—药剂学]