title: Dual ligand immunoliposomes for drug delivery to the brain.
abstract: Drug delivery systems that can reach brain areas affected by amyloid deposits are still underdeveloped. We propose pegylated liposomes functionalized with two antibodies, the anti-transferrin receptor monoclonal antibody (OX26MAb) and the anti-amyloid beta peptide antibody (19B8MAb), as nanocarriers of drugs for Alzheimer's disease therapy. Two distinct conjugation methods are investigated. In one formulation, the OX26MAb is conjugated to the tip of polyethylene glycol molecules through the maleimide group and the 19B8MAb is bound through the streptavidin-biotin complex. In the second system the conjugation reagents are swapped between the antibodies. Fluorescence spectroscopy experiments on porcine brain capillary endothelial cells show that the cellular uptake of the immunoliposomes is substantially more efficient if OX26MAb antibody is conjugated through the streptavidin-biotin complex instead of the maleimide group. The ability of the immunoliposomes to cross the blood brain barrier was established by in vivo studies in wild type rats. Our results demonstrate the importance of the conjugation method used to bind the antibody that targets the blood brain barrier to immunoliposomes for efficient drug delivery to the brain.
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, 4200-465 Porto, Portugal.
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, 4200-465 Porto, Portugal.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Gomes
authors.affiliation: Institute for Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, 69120 Heidelberg, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: Fricker
authors.affiliation: MiND - Modulating factors in Neurodegenerative Disorders Group, IBMC - Instituto de Biologia Celular e Molecular, I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cardoso
authors.affiliation: MiND - Modulating factors in Neurodegenerative Disorders Group, IBMC - Instituto de Biologia Celular e Molecular, I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Ribeiro
authors.affiliation: MiND - Modulating factors in Neurodegenerative Disorders Group, IBMC - Instituto de Biologia Celular e Molecular, I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; ICBAS- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Portugal; Faculty of Sciences of the University of Porto, 4169-007 Porto, Portugal.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Gaiteiro
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, 4200-465 Porto, Portugal.
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, 4200-465 Porto, Portugal.
authors.forename: Maria do Carmo
authors.initials: Mdo C
authors.lastname: Pereira
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg SE-41296, Sweden. Electronic address: sandra.rocha@chalmers.se.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rocha
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D008024:Ligands; D008081:Liposomes; D013552:Swine
chemical_list: D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes
keywords: Alzheimer’s disease; Brain targeting; Conjugation method; Drug delivery; Immunoliposomes