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

• Autor(a) principal: Gaspar, M. C.
• Data de Publicação: 2015
• Outros Autores: Sousa, João José Martins Simões, Pais, Alberto António Caria Canelas, Cardoso, O. M., Murtinho, Dina Maria Bairrada, Serra, M. E. S., Tewes, F., Olivier, J.-C.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/92842; https://doi.org/10.1016/j.ejpb.2015.07.010
• topic: Aerosol; Chitosan; Crosslinking agents; Cystic Fibrosis; Experimental design; Levofloxacin; Lung delivery; Microspheres; Anti-Bacterial Agents; Chitosan; Cross-Linking Reagents; Cystic Fibrosis; Drug Carriers; Drug Liberation; Humans; Levofloxacin; Microspheres; Particle Size; Powder Diffraction; Pseudomonas Infections; Pseudomonas aeruginosa; Respiratory Therapy; Spectroscopy, Fourier Transform Infrared; Surface Properties; Technology, Pharmaceutical

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.