title: Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer's Disease.
abstract: The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26.
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto 4500-465, Portugal. joana.loureiro@fe.up.pt.
authors.forename: Joana A
authors.initials: JA
authors.lastname: Loureiro
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto 4500-465, Portugal. up201306970@fe.up.pt.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Andrade
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto 4500-465, Portugal. bio12101@fe.up.pt.
authors.forename: Ana
authors.initials: A
authors.lastname: Duarte
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy of the University of Porto, Porto 4050-313, Portugal. rutepneves@gmail.com.
authors.forename: Ana Rute
authors.initials: AR
authors.lastname: Neves
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy of the University of Porto, Porto 4050-313, Portugal. fontes_joana@hotmail.com.
authors.forename: Joana Fontes
authors.initials: JF
authors.lastname: Queiroz
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy of the University of Porto, Porto 4050-313, Portugal. cdnunes@ff.up.pt.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Nunes
authors.affiliation: Laboratoire de la barrière hémato-encéphalique (LBHE), University Artois, EA 2465, Lens F-62300, France. emmanuel.sevin@univ-artois.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Sevin
authors.affiliation: Laboratoire de la barrière hémato-encéphalique (LBHE), University Artois, EA 2465, Lens F-62300, France. laurence.tilloy@univ-artois.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fenart
authors.affiliation: Laboratoire de la barrière hémato-encéphalique (LBHE), University Artois, EA 2465, Lens F-62300, France. fabien.gosselet@univ-artois.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gosselet
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto 4500-465, Portugal. mcoelho@fe.up.pt.
authors.forename: Manuel A N
authors.initials: MA
authors.lastname: Coelho
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto 4500-465, Portugal. mcsp@fe.up.pt.
authors.forename: Maria Carmo
authors.initials: MC
authors.lastname: Pereira
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D056604:Grape Seed Extract / Q000008:administration & dosage / Q000737:chemistry; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry*; D066329:Protein Aggregates / Q000187:drug effects; D066263:Protein Aggregation, Pathological / Q000188:drug therapy / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D027843:Vitis / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D056604:Grape Seed Extract; D018796:Immunoconjugates; D008055:Lipids; D010936:Plant Extracts; D066329:Protein Aggregates; D013267:Stilbenes; D000077185:Resveratrol
keywords: Alzheimer’s disease; antibodies; blood-brain barrier; drug delivery systems; grape extracts; immuno SLN; resveratrol