Frantiescoli Dimer1, Cristiane de Souza Carvalho-Wodarz1, Jörg Haupenthal2, Rolf Hartmann2,3, Claus-Michael Lehr4,5. 1. Department of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany. 2. Department of Drug Development and Optimization (DDOP), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany. 3. Pharmaceutical and Medical Chemistry, Campus C2.3, Saarland University, 66123, Saarbrücken, Germany. 4. Department of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany. claus-michael.lehr@helmholtz-hzi.de. 5. Biopharmacy and Pharmaceutical Technology, Department of Pharmacy, Saarland University, Saarbrücken, 66123, Germany. claus-michael.lehr@helmholtz-hzi.de.
Abstract
PURPOSE: The aim of this work was to develop clarithromycin microparticles (CLARI-MP) and evaluate their aerodynamic behavior, safety in bronchial cells and anti-bacterial efficacy. METHODS: Microparticles containing clarithromycin were prepared as dry powder carrier for inhalation, using leucine and chitosan. CLARI-MP were deposited on Calu-3 grown at air-interface condition, using the pharmaceutical aerosol deposition device on cell cultures (PADDOCC). Deposition efficacy, transport across the cells and cytotoxicity were determined. Anti-antibacterial effect was evaluated against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. RESULTS: Microparticles were of spherical shape, smooth surface and size of about 765 nm. Aerosolization performance showed a fine particle fraction (FPF) of 73.3%, and a mass median aerodynamic diameter (MMAD) of 1.8 μm. Deposition on Calu-3 cells using the PADDOCC showed that 8.7 μg/cm(2) of deposited powder were transported to the basolateral compartment after 24 h. The safety of this formulation is supported by the integrity of the cellular epithelial barrier and absence of toxicity, and the antimicrobial activity demonstrated for Gram positive and Gram negative bacteria. CONCLUSIONS: The appropriate aerodynamic properties and the excellent deposition on Calu-3 cells indicate that clarithromycin microparticles are suitable for administration via pulmonary route and are efficient to inhibit bacteria proliferation.
PURPOSE: The aim of this work was to develop clarithromycin microparticles (CLARI-MP) and evaluate their aerodynamic behavior, safety in bronchial cells and anti-bacterial efficacy. METHODS: Microparticles containing clarithromycin were prepared as dry powder carrier for inhalation, using leucine and chitosan. CLARI-MP were deposited on Calu-3 grown at air-interface condition, using the pharmaceutical aerosol deposition device on cell cultures (PADDOCC). Deposition efficacy, transport across the cells and cytotoxicity were determined. Anti-antibacterial effect was evaluated against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. RESULTS: Microparticles were of spherical shape, smooth surface and size of about 765 nm. Aerosolization performance showed a fine particle fraction (FPF) of 73.3%, and a mass median aerodynamic diameter (MMAD) of 1.8 μm. Deposition on Calu-3 cells using the PADDOCC showed that 8.7 μg/cm(2) of deposited powder were transported to the basolateral compartment after 24 h. The safety of this formulation is supported by the integrity of the cellular epithelial barrier and absence of toxicity, and the antimicrobial activity demonstrated for Gram positive and Gram negative bacteria. CONCLUSIONS: The appropriate aerodynamic properties and the excellent deposition on Calu-3 cells indicate that clarithromycin microparticles are suitable for administration via pulmonary route and are efficient to inhibit bacteria proliferation.
Authors: K de Bruijne; S Ebersviller; K G Sexton; S Lake; D Leith; R Goodman; J Jetters; G W Walters; M Doyle-Eisele; R Woodside; H E Jeffries; I Jaspers Journal: Inhal Toxicol Date: 2009-02 Impact factor: 2.724
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Authors: Jaekyu Shin; Daniel F Pauly; Julie A Johnson; Reginald F Frye Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2008-07-05 Impact factor: 3.205