title: Multifunctional LUV liposomes decorated for BBB and amyloid targeting - B. In vivo brain targeting potential in wild-type and APP/PS1 mice.
abstract: Multifunctional liposomes (mf-LIPs) having a curcumin-lipid ligand (to target amyloids) together with two ligands to target the transferrin, and the low-density apolipoprotein receptor of the blood-brain-barrier (BBB) on their surface, were previously studied (in vitro) as potential theranostic systems for Alzheimer's disease (AD) (Papadia et al., 2017, Eur. J. Pharm. Sciences; 101:140-148). Herein, the targeting potential of mf-LIPs was compared to that of BBB-LIPs (liposomes having only the two BBB-specific ligands) in FVB mice (normal), as well as in double transgenic mice (APP/PS1) and their corresponding littermates (WT), by live-animal (in vivo) and explanted organ (ex vivo) imaging. In FVB mice, the head-signals of mf-LIPs and BBB-LIPs are either similar, or signals from mf-LIP are higher, suggesting that the co-presence of the curcumin derivative on the liposome surface does not disturb the functionality of the BBB-specific ligands. Higher brain/liver+spleen ratios (ex vivo) were calculated post-injection of mf-LIP, compared to those found after BBB-LIP injection, due to the reduced distribution of mf-LIPs in the liver and spleen; showing that the curcumin ligand increases the stealth properties of liposomes by reducing their uptake by liver and spleen. The later effect is more pronounced when the density of the BBB-specific ligands on the mf-LIPs is 0.1mol%, compared to 0.2%, highlighting the importance of this parameter. When a high lipid dose (4mg/mouse) is injected in WT and APP/PS1 mice, the head-signals of mf-LIPs are significantly higher than those of BBB-LIPs, but no differences are observed between WT and APP/PS1 mice. However, after administration of a low liposome dose (0.05mg/mouse) of mf-LIPs, significant differences in the head-signals are found between WT and transgenic mice, highlighting the AD theranostic potential of the multifunctional liposomes, as well as the importance of the experimental parameters used in such in vivo screening studies.
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 for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio 26504, Greece.
authors.forename: Anastasios D
authors.initials: AD
authors.lastname: Giannou
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: Bio-Imaging Lab, University of Antwerp, 2610 Wilrijk, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Bigot
authors.affiliation: Bio-Imaging Lab, University of Antwerp, 2610 Wilrijk, Belgium.
authors.forename: Greejte
authors.initials: G
authors.lastname: Vanhoute
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: Bio-Imaging Lab, University of Antwerp, 2610 Wilrijk, Belgium.
authors.forename: Annemie
authors.initials: A
authors.lastname: Van der Linded
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; D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D016503:Drug Delivery Systems; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008822:Mice, Transgenic; D053764:Presenilin-1
chemical_list: D000682:Amyloid; D008081:Liposomes; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Brain; Curcumin; Liposome; Live imaging; Multifunctional; Nanoparticle