title: Inhalation Study of Mycobacteriophage D29 Aerosol for Mice by Endotracheal Route and Nose-Only Exposure.
abstract: BACKGROUND
  Lytic mycobacteriophage D29 has the potential for tuberculosis treatment including multidrug-resistant strains. The aims of this study are to investigate deposition and distribution of aerosolized phage D29 particles in naive Balb/C mice, together with pharmacokinetics and evaluation of acute lung injury.
  
  
  METHODS
  Pharmacokinetics and BALF (bronchoalveolar lavage fluids) were analyzed after administration of phage D29 aerosols by endotracheal route using Penn-century aerosolizer; Collison 6-jet and Spinning top aerosol nebulizers (STAG) were used to generate phage aerosols with different particle size distributions in nose-only inhalation experiments. After exposure, deposited amounts of phage D29 particles in respiratory tracts were measured, and deposition efficiencies were calculated. A typical path deposition model for mice was developed, and then comparisons were made between predictions and experimentally measured results.
  
  
  RESULTS
  Approximately 10% of aerosolized phages D29 reached lung of mouse for pulmonary delivery, and were completely eliminated until 72 h after administration. In contrast, about 0.1% of intraperitoneal injected phages reached the lung, and were almost eliminated at 12 h time point. The inflammation was hardly observed in lung according to the results of BALF analysis. The CMADs (count median aerodynamic diameters) of generated aerosol by Collison and STAG nebulizer were 0.8 μm and 1.5 μm, respectively. After nose-only exposure, measured deposition efficiencies in whole respiratory tract for 0.8 and 1.5 μm phage particles were below 1% and 10%, respectively. Predictions of the computer deposition model compared fairly well with experimentally measured results.
  
  
  CONCLUSIONS
  This is the first systematic study of phage D29 aerosol respiratory challenge in laboratory animals. It provides evidence that aerosol delivery of phage D29 is an effective way for treating pulmonary infections caused by Mycobacterium tuberculosis. This research will also provide important data for future inhalation experiments.
authors.affiliation: 1 Tongzhou Institute of Infectious Diseases and Epidemiology , Beijing, China .|2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Ke-Yang
authors.initials: KY
authors.lastname: Liu
authors.affiliation: 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Yang
authors.affiliation: 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Xiao-Kai
authors.initials: XK
authors.lastname: Dong
authors.affiliation: 1 Tongzhou Institute of Infectious Diseases and Epidemiology , Beijing, China .
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Cong
authors.affiliation: 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: 3 College of Veterinary Medicine, Nanjing Agricultural University , Nanjing, China .
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Zhan-Bo
authors.initials: ZB
authors.lastname: Wen
authors.affiliation: 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yin
authors.affiliation: 1 Tongzhou Institute of Infectious Diseases and Epidemiology , Beijing, China .
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Lan
authors.affiliation: 1 Tongzhou Institute of Infectious Diseases and Epidemiology , Beijing, China .
authors.forename: Wei-Peng
authors.initials: WP
authors.lastname: Li
authors.affiliation: 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology , Beijing, China .
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Li
keywords: D29; aerosol inhalation; computer model; deposition efficiency; mycobacteriophage; nose-only exposure; pulmonary delivery; respiratory tract; simulation