Liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide affect Aß aggregation features and cross the blood-brain-barrier: implications for therapy of Alzheimer disease.
Nanomedicine
; 10(7): 1583-90, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24333591
ABSTRACT
Targeting amyloid-ß peptide (Aß) within the brain is a strategy actively sought for therapy of Alzheimer's disease (AD). We investigated the ability of liposomes bi-functionalized with phosphatidic acid and with a modified ApoE-derived peptide (mApoE-PA-LIP) to affect Aß aggregation/disaggregation features and to cross in vitro and in vivo the blood-brain barrier (BBB). Surface plasmon resonance showed that bi-functionalized liposomes strongly bind Aß (kD=0.6 µM), while Thioflavin-T and SDS-PAGE/WB assays show that liposomes inhibit peptide aggregation (70% inhibition after 72 h) and trigger the disaggregation of preformed aggregates (60% decrease after 120 h incubation). Moreover, experiments with dually radiolabelled LIP suggest that bi-functionalization enhances the passage of radioactivity across the BBB either in vitro (permeability=2.5×10(-5) cm/min, 5-fold higher with respect to mono-functionalized liposomes) or in vivo in healthy mice. Taken together, our results suggest that mApoE-PA-LIP are valuable nanodevices with a potential applicability in vivo for the treatment of AD. From the clinical editor Bi-functionalized liposomes with phosphatidic acid and a modified ApoE-derived peptide were demonstrated to influence Aß aggregation/disaggregation as a potential treatment in an Alzheimer's model. The liposomes were able to cross the blood-brain barrier in vitro and in vivo. Similar liposomes may become clinically valuable nanodevices with a potential applicability for the treatment of Alzheimer's disease.
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MEDLINE
Assunto principal:
Apolipoproteínas E
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Peptídeos
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Ácidos Fosfatídicos
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Barreira Hematoencefálica
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Doença de Alzheimer
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Lipossomos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article