title: Intranasal delivery of human beta-amyloid peptide in rats: effective brain targeting.
abstract: (1) Intranasal administration is a non-invasive and effective way for the delivery of drugs to brain that circumvents the blood-brain barrier. The aims of the study were to test a nasal delivery system for human beta-amyloid (A beta) peptides, to measure the delivery of the peptides to brain regions, and to test their biological activity in rats. (2) A beta(1-42), in the form of a mixture of oligomers, protofibrils, and fibrils was dissolved in a nasal formulation containing hydrophobic, hydrophylic, and mucoadhesive components. The peptide solution was administered intranasally to rats as a single dose or in repeated doses. (3) Nasally injected A beta labeled with the blue fluorescent dye amino-methyl coumarinyl acetic acid (AMCA) could be detected by fluorescent microscopy in the olfactory bulb and frontal cortex. The concentration of the peptide was quantified by fluorescent spectroscopy, and a significant amount of AMCA-A beta peptide could be detected in the olfactory bulb. Unlabeled A beta also reached the olfactory bulb and frontal cortex of rats as evidenced by intense immunostaining. (4) In behavioral experiments, nasal A beta treatment did not affect anxiety levels (open-field test) and short-term memory (Y-maze test), but significantly impaired long-term spatial memory in the Morris water maze. The treatments did not result in A beta immunization. (5) The tested intranasal delivery system could successfully target a bioactive peptide into the central nervous system and provides a basis for developing a non-invasive and cost effective, new model to study amyloid-induced dysfunctions in the brain.
authors.affiliation: Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Sipos
authors.forename: Anita
authors.initials: A
authors.lastname: Kurunczi
authors.forename: András
authors.initials: A
authors.lastname: Fehér
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Penke
authors.forename: Lívia
authors.initials: L
authors.lastname: Fülöp
authors.forename: Agnes
authors.initials: A
authors.lastname: Kasza
authors.forename: János
authors.initials: J
authors.lastname: Horváth
authors.forename: Sándor
authors.initials: S
authors.lastname: Horvát
authors.forename: Szilvia
authors.initials: S
authors.lastname: Veszelka
authors.forename: Gábor
authors.initials: G
authors.lastname: Balogh
authors.forename: Levente
authors.initials: L
authors.lastname: Kürti
authors.forename: István
authors.initials: I
authors.lastname: Eros
authors.forename: Piroska
authors.initials: P
authors.lastname: Szabó-Révész
authors.forename: Arpád
authors.initials: A
authors.lastname: Párducz
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Mária A
authors.initials: MA
authors.lastname: Deli
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)