title: Suitability of a new antimicrobial aminosterol formulation for aerosol delivery in cystic fibrosis.
abstract: OBJECTIVE
  We evaluated the suitability of an aminosterol derivative (ASD), possessing interesting in vitro antimicrobial activities against various resistant pathogens involved in lung infections of cystic fibrosis patients, for aerosol drug delivery.
  
  
  METHODS
  The suitability of 2 and 10 mg/mL ASD solutions for aerosol delivery was evaluated and compared with that of a commercial inhalable solution of tobramycin using Pari LC Plus and eFlow rapid nebulizers. Physicochemical properties of ASD solutions, including pH and osmolarity, were assessed. The particle size distribution of the aerosols was analysed using a laser diffraction method. Effects of mucin on the in vitro antibacterial activities of ASD solutions and tobramycin were assessed using the broth dilution method for MIC determination.
  
  
  RESULTS
  MICs of ASD and tobramycin for Pseudomonas aeruginosa ATCC 27853 were 4 and 1 mg/L, respectively, and those for Staphylococcus aureus ATCC 25923 were 1 and 0.5 mg/L, respectively. MICs of tobramycin increased at least 4- and 16-fold for both bacteria after addition of mucin at 1 and 10 mg/mL, respectively, while MICs of ASD remained unchanged. ASD solutions should be prepared in 0.9% NaCl solution in order to produce an isotonic state, and need the addition of NaOH to give a suitable pH value for inhalation. ASD solutions were successfully nebulized using both nebulizers, as reflected by the similarity of the aerodynamic parameters to those of a commercial tobramycin solution.
  
  
  CONCLUSIONS
  This introductory study demonstrates the suitability of ASDs for aerosol delivery and calls for further work to evaluate such formulations using a lung-infected animal model.
authors.affiliation: URMITE UMR 6236, CNRS-IRD, Faculté de Médecine et de Pharmacie, Marseille, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Alhanout
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Brunel
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Dubus
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Rolain
authors.forename: Véronique
authors.initials: V
authors.lastname: Andrieu
mesh_terms: D000336:Aerosols / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy*; D002777:Cholestanols / Q000737:chemistry* / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000150:complications*; D004355:Drug Stability; D006801:Humans; D008826:Microbial Sensitivity Tests; D052638:Particulate Matter; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D002777:Cholestanols; D052638:Particulate Matter