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

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 96; pp. 65 - 75
• Main Authors: Gaspar, Marisa C., Sousa, João J.S., Pais, Alberto A.C.C., Cardoso, Olga, Murtinho, Dina, Serra, M. Elisa S., Tewes, Frédéric, Olivier, Jean-Christophe
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2015; Elsevier
• Subjects: Aerosol; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - therapeutic use; Chitosan; Chitosan - chemistry; Cross-Linking Reagents - chemistry; Crosslinking agents; Cystic Fibrosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis - microbiology; Drug Carriers - chemistry; Drug Liberation; Experimental design; Humans; Levofloxacin; Levofloxacin - administration & dosage; Levofloxacin - chemistry; Levofloxacin - therapeutic use; Life Sciences; Lung delivery; Microspheres; Particle Size; Pharmaceutical sciences; Powder Diffraction; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - isolation & purification; Pseudomonas Infections - drug therapy; Pseudomonas Infections - microbiology; Respiratory Therapy - methods; Spectroscopy, Fourier Transform Infrared; Surface Properties; Technology, Pharmaceutical - methods; EE; Levofloxacin; CF; Cystic Fibrosis; GL; MS; Aerosol; MMAD; DL; GNP; LVX; NGI; Microspheres; GLY; Experimental design; Crosslinking agents; Lung delivery; GA; Chitosan; FPF; CFTR; ED
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2015.07.010

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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.