Formulation of Bacteriophage for Inhalation to Treat Multidrug-Resistant Pulmonary Infections

Abstract

Rapid development of antibiotic resistance in pathogenic bacteria and a decline in the pharmaceutical development of new antibiotics are pushing the research community to explore alternative antimicrobials that can replace or complement antibiotics. Bacteriophages (or, phages) are naturally occurring viruses that can kill bacteria with high specificity and can evolve to target resistant bacteria. Phages have been historically employed as antimicrobial agents, but they were overshadowed by the emergence of antibiotics. With a renewed focus on phages, it is important to study their clinical efficacy, safety, and formulation. Pulmonary infections have a large burden of global morbidity and frequently involve multidrug-resistant pathogens such as Acinetobacter baumannii, Klebsiella pneumoniae, Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Therefore, this can be an important area of application of phages. Dry powder inhalers can be an effective strategy to deliver phages to the lungs because they are easy-to-use, portable, and capable of delivering a higher lung dose than oral or intravenous route. They also have longer shelf life and lower cold storage requirements than solutions. Therefore, the aim of the current review is to summarize recent findings on bacteriophage dry powder formulations, particularly focusing on the effect of various excipients and manufacturing factors on phage titer preservation.