title: Intranasal delivery of dopamine to the striatum using glycol chitosan/sulfobutylether-β-cyclodextrin based nanoparticles.
abstract: The aim of this study was to evaluate chitosan (CS)-, glycol chitosan (GCS)- and corresponding thiomer-based nanoparticles (NPs) for delivering dopamine (DA) to the brain by nasal route. Thus, the polyanions tripolyphosphate and sulfobutylether-β-cyclodextrin (SBE-β-CD), respectively, were used as polycation crosslinking agents and SBE-β-CD also in order to enhance the DA stability. The most interesting formulation, containing GCS and SBE-β-CD, was denoted as DA GCS/DA-CD NPs. NMR spectroscopy demonstrated an inclusion complex formation between SBE-β-CD and DA. X-ray photoelectron spectroscopy analysis revealed the presence of DA on the external surface of NPs. DA GCS/DA-CD NPs showed cytotoxic effect toward Olfactory Ensheathing Cells only at higher dosage. Acute administration of DA GCS/DA-CD NPs into the right nostril of rats did not modify the levels of the neurotransmitter in both right and left striatum. Conversely, repeated intranasal administration of DA GCS/DA-CD NPs into the right nostril significantly increased DA in the ipsilateral striatum. Fluorescent microscopy of olfactory bulb after acute administration of DA fluorescent-labeled GCS/DA-CD NPs into the right nostril showed the presence of NPs only in the right olfactory bulb and no morphological tissue damage occurred. Thus, these GCS based NPs could be potentially used as carriers for nose-to-brain DA delivery for the Parkinson's disease treatment.
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
authors.forename: Sante
authors.initials: S
authors.lastname: Di Gioia
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy. Electronic address: adriana.trapani@uniba.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Trapani
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Mandracchia
authors.affiliation: Department of Chemistry, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: De Giglio
authors.affiliation: Department of Chemistry, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cometa
authors.affiliation: Department of Chemistry, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mangini
authors.affiliation: Department of Chemistry, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Arnesano
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Belgiovine
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Castellani
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pace
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Roma, Piazzale A. Moro 5, 00185 Roma, Italy.
authors.forename: Michele Angelo
authors.initials: MA
authors.lastname: Lavecchia
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", via Orabona, 4, 70125 Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Trapani
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Conese
authors.affiliation: Laboratory of Drug Delivery Technology, Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Puglisi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Viale L. Pinto 1, 71122 Foggia, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000281:Administration, Intranasal; D000818:Animals; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003342:Corpus Striatum / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004298:Dopamine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D004355:Drug Stability; D004847:Epithelial Cells / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008856:Microscopy, Fluorescence; D050997:Nanomedicine; D053758:Nanoparticles; D009830:Olfactory Bulb / Q000378:metabolism; D009831:Olfactory Mucosa / Q000378:metabolism; D056951:Photoelectron Spectroscopy; D017208:Rats, Wistar; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D004337:Drug Carriers; D047392:beta-Cyclodextrins; C118638:glycol-chitosan; D015102:3,4-Dihydroxyphenylacetic Acid; C093196:SBE4-beta-cyclodextrin; D048271:Chitosan; D004298:Dopamine
keywords: Brain delivery; Chitosan (PubMed CID: 71853); Chitosan/glycol chitosan; Dihydroxyphenylacetic acid (PubMed CID: 547); Dopamine; Dopamine hydrochloride (PubMed CID: 65340); Fluorescein isothiocyanate (PubMed CID: 18730); Nanoparticles; Nasal administration; Noradrenaline (PubMed CID: 439260); Pentasodium tripolyphosphate (PubMed CID: 24455); XPS (X-ray photoelectron spectroscopy); l-Dopa (PubMed CID: 6047); β-Cyclodextrin (PubMed CID: 444041)