Abstract
The aim of this study was to evaluate the storage stability of inhalable phage powders containing lactose and leucine as excipient. As an FDA-approved excipient for inhalation, lactose is preferred over other sugars. PEV phages active against antibiotic-resistant Pseudomonas aeruginosa was spray dried with lactose (55-90%) and leucine (45-10%). Produced powders were heat-sealed in an aluminium pouch at 15% relative humidity (RH) with subsequent storage at 20 °C/60% RH for 12 months. Lactose concentration in the powder positively influenced the phage stability over time. Formulation containing 90% lactose maintained the viability of PEV61 across the study, while ∼1.2 log(10) titer reduction was observed in formulations with less lactose. PEV20 was more prone to inactivation (1.7 log(10) titer loss at 12-month) when lactose concentration in the particle was below 80%. The fine particle fraction (% wt. particles <5 μm in aerosol) of phage powders was 52-61% and remained the same after 12-month storage. The results demonstrate that spray dried PEV phage powders containing lactose and leucine are biologically and physically stable over long-term storage at ambient temperature. Furthermore, these spray dried phage powders were shown to be non-toxic to lung alveolar macrophage and epithelial cells in vitro.