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 107 to 108 pfu, levels that are expected to be efficacious in vivo. Spray drying of bacteriophages into a respirable dry powder was found to be feasible.