Use of functionalized liposomes loaded with antioxidants to permeate the blood–brain barrier and inhibit β-amyloid-induced neurodegeneration in the brain
Autor: | Yung-Chih Kuo, Rajendiran Rajesh, I-Yin Chen |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Apolipoprotein E Liposome General Chemical Engineering Neurodegeneration Neurotoxicity 02 engineering and technology General Chemistry Phosphatidic acid Pharmacology 021001 nanoscience & nanotechnology Blood–brain barrier medicine.disease 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology medicine.anatomical_structure chemistry medicine 0210 nano-technology Drug carrier Lipoprotein |
Zdroj: | Journal of the Taiwan Institute of Chemical Engineers. 87:1-14 |
ISSN: | 1876-1070 |
Popis: | 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 β-amyloid (1–42) (Aβ1-42)-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 Aβ1-42-insulted SK-N-MC cells. In anin vivo AD model, ApoE-QU-RA-PA-liposomes decreased acetylcholinesterase activity and lipid peroxidation level, and lowered Aβ 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 Aβ1-42-induced neurotoxicity. |
Databáze: | OpenAIRE |
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