Spray-dried respirable powders containing bacteriophages for the treatment of pulmonary infections.
Myoviridae bacteriophages were processed into a dry powder inhalable dosage form using a low-temperature spray-drying process. The phages were incorporated into microparticles consisting of trehalose, leucine, and optionally a third excipient (either a surfactant or casein sodium salt). The particles were designed to have high dispersibility and a respirable particle size, and to preserve the phages during processing. Bacteriophages KS4- M, KS14, and cocktails of phages ΦKZ/D3 and ΦKZ/D3/KS4-M were spray-dried with a processing loss ranging from 0.4 to 0.8 log pfu. The aerosol performance of the resulting dry powders as delivered from an Aerolizer® dry powder inhaler (DPI) exceeded the performance of commercially available DPIs; the emitted mass and the in vitro total lung mass of the lead formulation were 82.7% and 69.7% of filled capsule mass, respectively. The total lung mass had a mass median aerodynamic diameter of 2.5-2.8 µm. The total in vitro lung doses of the phages, delivered from a single actuation of the inhaler, ranged from 10(7) to 10(8) pfu, levels that are expected to be efficacious in vivo. Spray drying of bacteriophages into a respirable dry powder was found to be feasible.
Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta T6G 2G8, Canada.
Sadaf
S
Matinkhoo
Karlene H
KH
Lynch
Jonathan J
JJ
Dennis
Warren H
WH
Finlay
Reinhard
R
Vehring
D000280:Administration, Inhalation; D000336:Aerosols; D001435:Bacteriophages / Q000737:chemistry / Q000502:physiology*; D002364:Caseins / Q000737:chemistry; D003890:Desiccation; D004339:Drug Compounding; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry; D006801:Humans; D008168:Lung; D008171:Lung Diseases / Q000628:therapy*; D017900:Myoviridae; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011208:Powders / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use; D011550:Pseudomonas aeruginosa / Q000821:virology; D012141:Respiratory Tract Infections / Q000628:therapy*; D013501:Surface-Active Agents / Q000737:chemistry; D014199:Trehalose / Q000737:chemistry
D000336:Aerosols; D002364:Caseins; D005079:Excipients; D011208:Powders; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D014199:Trehalose; C016811:tyloxapol