title: Sodium hyaluronate as a mucoadhesive component in nasal formulation enhances delivery of molecules to brain tissue.
abstract: Intranasal administration of molecules has been investigated as a non-invasive way for delivery of drugs to the brain in the last decade. Circumvention of both the blood-brain barrier and the first-pass elimination by the liver and gastrointestinal tract is considered as the main advantages of this method. Because of the rapid mucociliary clearance in the nasal cavity, bioadhesive formulations are needed for effective targeting. Our goal was to develop a formulation containing sodium hyaluronate, a well-known mucoadhesive molecule, in combination with a non-ionic surfactant to enhance the delivery of hydrophilic compounds to the brain via the olfactory route. Fluorescein isothiocyanate-labeled 4 kDa dextran (FD-4), used as a test molecule, was administered nasally in different formulations to Wistar rats, and detected in brain areas by fluorescent spectrophotometry. Hyaluronan increased the viscosity of the vehicles and slowed down the in vitro release of FD-4. Significantly higher FD-4 transport could be measured in the majority of brain areas examined, including olfactory bulb, frontal and parietal cortex, hippocampus, cerebellum, midbrain and pons, when the vehicle contained hyaluronan in combination with absorption enhancer. The highest concentrations of FD-4 could be detected in the olfactory bulbs, frontal and parietal cortex 4h after nasal administration in the mucoadhesive formulation. Intravenous administration of a hundred times higher dose of FD-4 resulted in a lower brain penetration as compared to nasal formulations. Morphological examination of the olfactory system revealed no toxicity of the vehicles. Hyaluronan, a non-toxic biomolecule used as a mucoadhesive in a nasal formulation, increased the brain penetration of a hydrophilic compound, the size of a peptide, via the nasal route.
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary; Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Horvát
authors.forename: András
authors.initials: A
authors.lastname: Fehér
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.forename: Péter
authors.initials: P
authors.lastname: Sipos
authors.forename: Szilvia
authors.initials: S
authors.lastname: Veszelka
authors.forename: Andrea
authors.initials: A
authors.lastname: Tóth
authors.forename: Lóránd
authors.initials: L
authors.lastname: Kis
authors.forename: Anita
authors.initials: A
authors.lastname: Kurunczi
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: Mária A
authors.initials: MA
authors.lastname: Deli
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology / Q000379:methods; D013050:Spectrometry, Fluorescence / Q000379:methods; D014018:Tissue Distribution
chemical_list: D003911:Dextrans; D004337:Drug Carriers; C015219:fluorescein isothiocyanate dextran; D006820:Hyaluronic Acid; D016650:Fluorescein-5-isothiocyanate