title: Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections.
abstract: The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders.
  
  
  
  A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1 = 60:20:20 and F2 = 40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed.
  
  
  
  A significant titer loss (~2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1 = 13.1 ± 1.7 × 10(4) pfu and SD-F2 = 11.0 ± 1.4 × 10(4) pfu) than from their counterpart SFD formulations (SFD-F1 = 8.3 ± 1.8 × 10(4) pfu and SFD-F2 = 2.1 ± 0.3 × 10(4) pfu).
  
  
  
  Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2.
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Sharon S Y
authors.initials: SS
authors.lastname: Leung
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Thaigarajan
authors.initials: T
authors.lastname: Parumasivam
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Fiona G
authors.initials: FG
authors.lastname: Gao
authors.affiliation: Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, T6G 2G8, Canada.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Carrigy
authors.affiliation: Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, T6G 2G8, Canada.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Vehring
authors.affiliation: Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, T6G 2G8, Canada.
authors.forename: Warren H
authors.initials: WH
authors.lastname: Finlay
authors.affiliation: AmpliPhi Biosciences AU, 7/27 Dale Street, Brookvale, Sydney, NSW, 2100, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Morales
authors.affiliation: Tuberculosis Research Program, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
authors.affiliation: The Evergreen State College, Olympia, Washington, 98502, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kutter
authors.affiliation: Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia. kim.chan@sydney.edu.au.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D005612:Freeze Drying / Q000379:methods*; D007930:Leucine / Q000737:chemistry; D008168:Lung / Q000382:microbiology / Q000821:virology*; D008353:Mannitol / Q000737:chemistry; D050296:Microbial Viability; D009330:Nebulizers and Vaporizers; D000071059:Phage Therapy / Q000379:methods*; D017902:Podoviridae / Q000472:pathogenicity*; D011208:Powders; D011549:Pseudomonas / Q000472:pathogenicity / Q000821:virology*; D011552:Pseudomonas Infections / Q000382:microbiology / Q000628:therapy* / Q000821:virology; D012141:Respiratory Tract Infections / Q000382:microbiology / Q000628:therapy* / Q000821:virology; D014199:Trehalose / Q000737:chemistry; D014465:Ultrasonics
chemical_list: D000336:Aerosols; D011208:Powders; D008353:Mannitol; D014199:Trehalose; D007930:Leucine
keywords: aerosols; antibiotic-resistant bacteria; phage therapy; pulmonary infections