期刊
JOURNAL OF THE TAIWAN INSTITUTE OF CHEMICAL ENGINEERS
卷 87, 期 -, 页码 1-14出版社
ELSEVIER
DOI: 10.1016/j.jtice.2018.03.001
关键词
Surface modification; Liposome; Alzheimer's disease; Acetylcholinesterase; Lipid peroxidation
资金
- Ministry of Science and Technology of the Republic of China
Effective treatment methods for neurodegenerative disorders in the central nervous system are still facing a great many hurdles due to inability of drugs to permeate the blood-brain barrier (BBB). In this study, a drug carrier system of apolipoprotein E (ApoE)-modified liposomes conjugated with phosphatidic acid (PA) was fabricated to improve BBB penetration and release quercetin (QU) and rosmarinic acid (RA) to inhibit beta-amyloid (1-42) (A beta(1-42))-induced Alzheimer's disease (AD). An in vitro BBB model validated the enhanced ability of the dual-functioning ApoE-QU-RA-PA-liposomes to infiltrate the BBB and preserve high viability of endothelia, compared with Tween 80-QU-RA-PA-liposomes. Immunochemical staining images exhibited evidence that ApoE-QU-RA-PA-liposomes were able to penetrate the BBB through the aid of strong attractions between ApoE and low-density lipoprotein receptors in brain microvascular endothelial cells, and also inhibited the apoptosis of A beta(1-42)-insulted SK-N-MC cells. In an in vivo AD model, ApoE-QU-RA-PA-liposomes decreased acetylcholinesterase activity and lipid peroxidation level, and lowered Ap plaque formation. The surface functionalization of liposomes using PA and ApoE can be a promising approach to crossing the BBB and delivering QU and RA to the brain in management of A beta(1-42)-induced neurotoxicity. (C) 2018 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
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