title: Optimization of levofloxacin-loaded crosslinked chitosan microspheres for inhaled aerosol therapy.
abstract: The aim of this work was the development of innovative levofloxacin-loaded swellable microspheres (MS) for the dry aerosol therapy of pulmonary chronicPseudomonas aeruginosainfections in Cystic Fibrosis patients. In a first step, a factorial design was applied to optimize formulations of chitosan-based MS with glutaraldehyde as crosslinker. After optimization, other crosslinkers (genipin, glutaric acid and glyceraldehyde) were tested. Analyses of MS included aerodynamic and swelling properties, morphology, drug loading, thermal and chemical characteristics,in vitroantibacterial activity and drug release studies. The prepared MS presented a drug content ranging from 39.8% to 50.8% of levofloxacin in an amorphous or dispersed state, antibacterial activity and fast release profiles. The highest degree of swelling was obtained for MS crosslinked with glutaric acid and genipin. These formulations also presented satisfactory aerodynamic properties, making them a promising alternative, in dry-powder inhalers, to levofloxacin solution for inhalation.
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal; Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: mgaspar@ff.uc.pt.
authors.forename: Marisa C
authors.initials: MC
authors.lastname: Gaspar
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal; Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: João J S
authors.initials: JJ
authors.lastname: Sousa
authors.affiliation: Chemistry Department, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Alberto A C C
authors.initials: AA
authors.lastname: Pais
authors.affiliation: Laboratory of Microbiology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: Olga
authors.initials: O
authors.lastname: Cardoso
authors.affiliation: Chemistry Department, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: Dina
authors.initials: D
authors.lastname: Murtinho
authors.affiliation: Chemistry Department, University of Coimbra, 3004-535 Coimbra, Portugal.
authors.forename: M Elisa S
authors.initials: ME
authors.lastname: Serra
authors.affiliation: INSERM, U 1070, Pôle Biologie Santé, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9, France; University of Poitiers, Faculty of Medicine and Pharmacy, 6 rue de la Milétrie, TSA 51115, 86073 Poitiers Cedex 9, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Tewes
authors.affiliation: INSERM, U 1070, Pôle Biologie Santé, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9, France; University of Poitiers, Faculty of Medicine and Pharmacy, 6 rue de la Milétrie, TSA 51115, 86073 Poitiers Cedex 9, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Olivier
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D048271:Chitosan / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D064704:Levofloxacin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008863:Microspheres; D010316:Particle Size; D033362:Powder Diffraction; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D012138:Respiratory Therapy / Q000379:methods*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D064704:Levofloxacin; D048271:Chitosan
keywords: Aerosol; Chitosan; Crosslinking agents; Cystic Fibrosis; Experimental design; Levofloxacin; Lung delivery; Microspheres