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Title: Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of ECGC in a APPswe/PS1dE9 Alzheimer's disease mice model.
Author: Cano Fernández, Amanda
Ettcheto Arriola, Miren
Chang, Jui-Hsien
Barroso Fernández, Emma
Espina García, Marta
Kühne, Britta A.
Barenys Espadaler, Marta
Auladell i Costa, M. Carme
Folch, Jaume
Souto, Eliana B.
Camins Espuny, Antoni
Turowski, Patrick
García López, María Luisa
Keywords: Malaltia d'Alzheimer
Alzheimer's disease
Issue Date: 13-Mar-2019
Publisher: Elsevier B.V.
Abstract: Epigallocatechin-3-gallate (EGCG) is a candidate for treatment of Alzheimer's disease (AD) but its inherent instability limits bioavailability and effectiveness. We found that EGCG displayed increased stability when formulated as dualdrug loaded PEGylated PLGA nanoparticles (EGCG/AA NPs). Oral administration of EGCG/AA NPs in mice resulted in EGCG accumulation in all major organs, including the brain. Pharmacokinetic comparison of plasma and brain accumulation following oral administration of free or EGCG/AA NPs showed that, whilst in both cases initial EGCG concentrations were similar, long-term (5-25 h) concentrations were ca. 5 fold higher with EGCG/AA NPs. No evidence was found that EGCG/AA NPs utilised a specific pathway across the blood-brain barrier (BBB). However, EGCG, empty NPs and EGCG/AA NPs all induced tight junction disruption and opened the BBB in vitro and ex vivo. Oral treatment of APPswe/PS1dE9 (APP/PS1) mice, a familial model of AD, with EGCG/AA NPs resulted in a marked increase in synapses, as judged by synaptophysin (SYP) expression, and reduction of neuroinflammation as well as amyloid β (Aβ) plaque burden and cortical levels of soluble and insoluble Aβ(1-42) peptide. These morphological changes were accompanied by significantly enhanced spatial learning and memory. Mechanistically, we propose that stabilisation of EGCG in NPs complexes and a destabilized BBB led to higher therapeutic EGCG concentrations in the brain. Thus EGCG/AA NPs have the potential to be developed as a safe and strategy for the treatment of AD.
Note: Versió postprint del document publicat a:
It is part of: Journal of Controlled Release, 2019, vol. 301, p. 62-75
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ISSN: 0168-3659
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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