Multifunctional nanoliposomes with curcumin-lipid derivative and brain targeting functionality with potential applications for Alzheimer disease.
With the objective to formulate multifunctional nanosized liposomes to target amyloid deposits in Alzheimer Disease (AD) brains, a lipid-PEG-curcumin derivative was synthesized and characterized. Multifunctional liposomes incorporating the curcumin derivative and additionally decorated with a Blood Brain Barrier (BBB) transport mediator (anti-Transferin antibody) were prepared and characterized. The fluorescence intensity of curcumin derivative was found to increase notably when the curcumin moiety was in the form of a diisopropylethylamine (DIPEA) salt. Both curcumin-derivative liposomes and curcumin-derivative Anti-TrF liposomes showed a high affinity for the amyloid deposits, on post-mortem brains samples of AD patients. The ability of both liposomes to delay Aβ1-42 peptide aggregation was confirmed by Thioflavin assay. However, the decoration of the curcumin-derivative liposomes with the Anti-TrF improved significantly the intake by the BBB cellular model. Results verify that the attachment of an antibody on the curcumin-liposome surface does not block deposit staining or prevention of Aβ aggregation, while the presence of the curcumin-PEG-lipid conjugate does not reduce their brain-targeting capability substantially, proving the potential of such multifunctional NLs for application in Alzheimer disease treatment and diagnosis.
Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, Rio 26510, Greece.
Spyridon
S
Mourtas
Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, 47 Bd de l'hôpital 75013 Paris, France; Centre de recherche de l'ICM, (UPMC, INSERM UMR S 975, CNRS UMR 7225), 47 Bd de l'hôpital, 75013 Paris, France.
Adina N
AN
Lazar
Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, Rio 26510, Greece.
Eleni
E
Markoutsa
Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, 47 Bd de l'hôpital 75013 Paris, France; Centre de recherche de l'ICM, (UPMC, INSERM UMR S 975, CNRS UMR 7225), 47 Bd de l'hôpital, 75013 Paris, France.
Charles
C
Duyckaerts
Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, Rio 26510, Greece; Institute of Chemical Engineering Sciences, FORTH/ICES, Rio, 26504 Patras, Greece. Electronic address: santimis@upatras.gr.
Sophia G
SG
Antimisiaris
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D011092:Polyethylene Glycols; D003474:Curcumin
Amyloid; Curcumin; Liposome; Multifunctional; Nanoparticle; Targeting