Phage cocktail broadens the host range compared with a single phage and minimizes the development of phage-resistant bacteria thereby promoting the long-term usefulness of inhaled phage therapy. In this study, we produced a phage cocktail powder by spray drying three Pseudomonas phages PEV2 (podovirus), PEV1 and PEV20 (both myovirus) with lactose (80 wt%) and leucine (20 wt%) as excipients. Our results showed that the phages remained viable in the spray dried powder, with little to mild titer reduction (ranging from 0.11 to 1.3 logs) against each of their specific bacterial strains. The powder contained spherical particles with a small volume median diameter of 1.9 µm (span 1.5), a moisture content of 3.5 ± 0.2 wt%., and was largely amorphous with some crystalline peaks, which were assigned to the excipient leucine, as shown in the X-ray diffraction pattern. When the powder was dispersed using the low- and high-resistance Osmohalers, the fine particle fraction (FPF, wt. % of particles < 5 µm in the aerosols relative to the loaded dose) values were 45.37 ± 0.27% and 62.69 ± 2.1% at the flow rate of 100 and 60 L/min, respectively. In conclusion, the PEV phage cocktail powder produced was stable, inhalable and efficacious in vitro against various MDR P. aeruginosa strains that cause pulmonary infections. This formulation will broaden the bactericidal spectrum and reduce the emergence of resistance in bacteria compared with single-phage formulations reported previously.
Keywords: Inhalation aerosol; Inhalation drug delivery; Lung infection; Phage combination; Phage therapy; Powder aerosol; Pulmonary infections.
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