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• W3048593560 endingPage "1590" @default.
• W3048593560 startingPage "1590" @default.
• W3048593560 abstract "Alzheimer’s disease (AD) is an age-related disease caused by abnormal accumulation of amyloid-β in the brain leading to progressive tissue degeneration. Flurbiprofen (FP), a drug used to mitigate the disease progression, has low efficacy due to its limited permeability across the blood–brain barrier (BBB). In a previous work, FP was coupled at the uppermost branching of an ε-lysine-based branched carrier, its root presenting a phenylalanine moiety able to increase the hydrophobicity of the complex and enhance the transport across the BBB by adsorptive-mediated transcytosis (AMT). The present study explores a different molecular design of the FP-peptide delivery system, whereby its root presents an ApoE-mimicking peptide, a targeting ligand that could enhance transport across the BBB by receptor-mediated transcytosis (RMT). The functionalised complex was synthesised using a solid-phase peptide synthesis and characterised by mass spectrometry and FTIR. Cytotoxicity and permeability of this complex across an in vitro BBB model were analysed. Moreover, its activity and degradation to release the drug were investigated. The results revealed successful synthesis and grafting of FP molecules at the uppermost molecular branches of the lysine terminal without observed cytotoxicity. When covalently linked to the nanocarrier, FP was still active on target cells, albeit with a reduced activity, and was released as a free drug upon hydrolysis in a lysosome-mimicking medium. Noticeably, this work shows the high efficiency of RMT-driven FP delivery over delivery systems relying on AMT." @default.
• W3048593560 created "2020-08-18" @default.
• W3048593560 creator A5017054405 @default.
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• W3048593560 creator A5083868259 @default.
• W3048593560 date "2020-08-13" @default.
• W3048593560 modified "2023-10-07" @default.
• W3048593560 title "A Peptide-Based Nanocarrier for an Enhanced Delivery and Targeting of Flurbiprofen into the Brain for the Treatment of Alzheimer’s Disease: An In Vitro Study" @default.
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• W3048593560 doi "https://doi.org/10.3390/nano10081590" @default.
• W3048593560 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7466704" @default.
• W3048593560 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32823499" @default.
• W3048593560 hasPublicationYear "2020" @default.
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