Optimization of levofloxacin-loaded crosslinked chitosan microspheres for inhaled aerosol therapy.

Marisa C Gaspar, João J S Sousa, Alberto A C C Pais, Olga Cardoso, Dina Murtinho, M Elisa S Serra, Frédéric Tewes, Jean-Christophe Olivier

Index: Eur. J. Pharm. Biopharm. 96 , 65-75, (2015)

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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. Copyright © 2015 Elsevier B.V. All rights reserved.