Optimizing Performance of Inhalable Bacteriophage Powders using Human Serum Albumin (HSA)

In response to the growing threat of antibiotic resistance in pulmonary infections, bacteriophage therapy is emerging as a promising alternative to traditional antibiotics. We aimed to develop novel dry powder formulations for the pulmonary delivery of bacteriophages, using the Pseudomonas aeruginosa-specific phage PEV2 as a model. Our formulations combined human serum albumin (HSA) and lactose to enhance both phage stability and aerosol performance. A Box-Behnken experimental design was conducted to investigate the effects of HSA/lactose ratio, solute concentration of feed solution, and spray-drying inlet temperature. Our results demonstrated that incorporating 60% w/w HSA significantly improved aerosol performance by achieving a fine particle fraction above 50% and effectively delayed lactose recrystallization by maintaining an amorphous state at relative humidity levels of 80% or higher. Importantly, the optimized formulation (60% HSA/40% lactose) preserved phage viability with less than a 0.8 log₁₀ reduction. Possible mechanisms contributing to stabilizing the phage powder formulations in HSA-lactose were discussed. These findings underscore the potential of a balanced HSA-lactose system as a robust powder formulation platform for pulmonary phage therapy.