title: In vitro lung delivery of bacteriophages KS4-M and ΦKZ using dry powder inhalers for treatment of Burkholderia cepacia complex and Pseudomonas aeruginosa infections in cystic fibrosis.
abstract: OBJECTIVE
  To determine the feasibility of formulating and aerosolizing powders containing bacteriophages KS4-M and ΦKZ for lung delivery and treatment of pulmonary Burkholderia cepacia complex and Pseudomonas aeruginosa infections.
  
  
  RESULTS
  Endotoxin-removed bacteriophages KS4-M and ΦKZ were lyophilized in lactose/lactoferrin 60 : 40 w/w matrix and deagglomerated in a mixer mill (without beads) to formulate respirable powders. The powders were then aerosolized using an Aerolizer(®) capsule inhaler. Mass median aerodynamic diameter (MMAD) of this inhalable aerosol was determined using Andersen cascade impactor at 60 l min(-1). Measured MMAD for both types of powders was 3·4 μm, and geometric standard deviation was 1·9-2·0. Viability of bacteriophages delivered distal to an idealized mouth-throat replica was determined from bioassays of samples collected on filters placed after the idealized replica. As a percentage of inhaler load, amount of powder delivered distal to the mouth-throat replica, which is a measure of lung delivery, was 33·7 ± 0·3% for KS4-M and 32·7 ± 0·9% for ΦKZ. Titres collected downstream of the mouth throat were (3·4 ± 2·5) × 10(6) PFU for KS4-M with an Aerolizer capsule load of (9·8 ± 4·8) × 10(6) and (1·9 ± 0·6) × 10(7) for ΦKZ with an Aerolizer capsule load of (6·5 ± 1·9) × 10(7).
  
  
  CONCLUSIONS
  Bacteriophages KS4-M and ΦKZ can be lyophilized without significant loss of viability in a lactose/lactoferrin 60 : 40 w/w matrix. The resulting powders can be aerosolized to deliver viable bacteriophages to the lungs.
  
  
  CONCLUSIONS
  Development of lactoferrin-based bacteriophage aerosol powders solidifies the ground for future research on developing novel formulations as an alternative to inhaled antibiotic therapy in patients with cystic fibrosis.
authors.affiliation: University of Alberta, Edmonton, AB, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Golshahi
authors.forename: K H
authors.initials: KH
authors.lastname: Lynch
authors.forename: J J
authors.initials: JJ
authors.lastname: Dennis
authors.forename: W H
authors.initials: WH
authors.lastname: Finlay
mesh_terms: D000336:Aerosols; D001435:Bacteriophages / Q000648:ultrastructure; D019121:Burkholderia Infections / Q000628:therapy*; D042602:Burkholderia cepacia complex; D003550:Cystic Fibrosis / Q000150:complications*; D058995:Dry Powder Inhalers; D005612:Freeze Drying; D006801:Humans; D007781:Lactoferrin / Q000032:analysis; D008168:Lung; D009330:Nebulizers and Vaporizers; D011552:Pseudomonas Infections / Q000628:therapy*; D011550:Pseudomonas aeruginosa
chemical_list: D000336:Aerosols; D007781:Lactoferrin