title: Multifunctional LUV liposomes decorated for BBB and amyloid targeting. A. In vitro proof-of-concept.
abstract: Multifunctional LUV liposomes (mf-LIPs) were developed, having a curcumin-lipid ligand (TREG) with affinity towards amyloid species, together with ligands to target the transferrin and the LDL receptors of the blood-brain-barrier (BBB), on their surface. mf-LIPs were evaluated for their brain targeting, on hCMEC/D3 monolayers, and for their ability to inhibit Aβ-peptide aggregation. The transport of mf-LIP across hCMEC/D3 monolayers was similar to that of BBB-LIPs, indicating that the presence of TREG on their surface does not reduce their brain targeting potential. Likewise, mf-LIP inhibitory effect on Aβ aggregation was similar to that of LIPs functionalized only with TREG, proving that the presence of brain targeting ligands does not reduce the functionality of the amyloid-specific ligand. Addition of the curcumin-lipid in some liposome types was found to enhance their integrity and reduce the effect of serum proteins on their interaction with brain endothelial cells. Finally, preliminary in vivo results confirm the in vitro findings. Concluding, the current results reveal the potential of the specific curcumin-lipid derivative as a component of multifunctional LIPs with efficient brain targeting capability, intended to act as a theragnostic system for AD.
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Papadia
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Markoutsa
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Mourtas
authors.affiliation: Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio 26504, Greece.
authors.forename: Anastassios D
authors.initials: AD
authors.lastname: Giannou
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza dellaScienza 2, 20126 Milan, Italy.
authors.forename: Barabara
authors.initials: B
authors.lastname: La Ferla
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza dellaScienza 2, 20126 Milan, Italy.
authors.forename: Fransesco
authors.initials: F
authors.lastname: Nicotra
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Istituto di RicercheFarmacologiche "Mario Negri", Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece; Institute of Chemical Engineering Sciences, FORTH/ICE-HT, Rio 26504, Greece.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Klepetsanis
authors.affiliation: Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio 26504, Greece; Comprehensive Pneumology Center (CPC), Institute for Lung Biology and Disease (iLBD), University Hospital, Ludwig-Maximilians University, Helmholtz Zentrum München (DZL), Munich, Bavaria 81377, Germany.
authors.forename: Georgios T
authors.initials: GT
authors.lastname: Stathopoulos
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece; Institute of Chemical Engineering Sciences, FORTH/ICE-HT, Rio 26504, Greece. Electronic address: santimis@upatras.gr.
authors.forename: Sophia G
authors.initials: SG
authors.lastname: Antimisiaris
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D014168:Transferrin / Q000378:metabolism
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D008081:Liposomes; D014168:Transferrin; D003474:Curcumin
keywords: Brain; Curcumin; Liposomes; Nanoparticle; Targeting