title: Inhalable Clarithromycin Microparticles for Treatment of Respiratory Infections.
abstract: OBJECTIVE
  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.affiliation: Department of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany.
authors.forename: Frantiescoli
authors.initials: F
authors.lastname: Dimer
authors.affiliation: Department of Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, 66123, Saarbrücken, Germany.
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Souza Carvalho-Wodarz
authors.affiliation: 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.
authors.forename: Jörg
authors.initials: J
authors.lastname: Haupenthal
authors.affiliation: 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.|Pharmaceutical and Medical Chemistry, Campus C2.3, Saarland University, 66123, Saarbrücken, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Hartmann
authors.affiliation: 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.|Biopharmacy and Pharmaceutical Technology, Department of Pharmacy, Saarland University, Saarbrücken, 66123, Germany. claus-michael.lehr@helmholtz-hzi.de.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D017291:Clarithromycin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D058995:Dry Powder Inhalers; D004926:Escherichia coli / Q000187:drug effects*; D004927:Escherichia coli Infections / Q000188:drug therapy; D006801:Humans; D010316:Particle Size; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D012995:Solubility; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin
keywords: aerosol; dry powder inhaler; lung infection; safety