title: Cellular uptake of PLGA nanoparticles targeted with anti-amyloid and anti-transferrin receptor antibodies for Alzheimer's disease treatment.
abstract: During the last few decades, relevant efforts have been reported to design nanocarriers for drug transport through the blood brain barrier (BBB). New drugs, such as peptide iAβ5, capable to inhibit the aggregates associated with Alzheimeŕs disease (AD) are being tested but the most frequent drawback is to reach the brain in the desired concentrations due to the low BBB permeability-surface area. Our approach, as a proof of concept to improve drug transport through the BBB, is based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles with surface functionalized with anti-transferrin receptor monoclonal antibody (OX26) and anti-Aβ (DE2B4) to deliver encapsulated iAβ5 into the brain. Porcine brain capillary endothelial cells (PBCECs) were used as a BBB model to evaluate the system efficacy and toxicity. The uptake of immune nanoparticles with a controlled delivery of the peptide iAβ5 was substantially increased compared to the nanoparticles (NPs) without monoclonal antibody functionalization.
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: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, 4200-465 Porto, Portugal.
authors.forename: Manuel A N
authors.initials: MAN
authors.lastname: Coelho
authors.affiliation: Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg SE-41296, Sweden.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rocha
authors.affiliation: LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, 4200-465 Porto, Portugal. Electronic address: mcsp@fe.up.pt.
authors.forename: Maria Carmo
authors.initials: MC
authors.lastname: Pereira
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000682:Amyloid / Q000037:antagonists & inhibitors*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors*; D013552:Swine
chemical_list: D000682:Amyloid; D000906:Antibodies; D011990:Receptors, Transferrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Alzheimer’s disease; Antibodies; Blood brain-barrier; Drug delivery systems; Immuno nanoparticles; Therapeutic peptides