A freeze-dried formulation of bacteriophage encapsulated in biodegradable microspheres

With the emergence of widespread antibiotic resistance, there has been renewed interest in the use of bacteriophages. While their potency, safety and specificity have underpinned their clinical potential, to date, little work has been focussed on their formulation with respect to controlled release and/or passive targeting. Here, we show that bacteriophages selective for Staphylococcus aureus or Pseudomonas aeruginosa can be encapsulated into biodegradable polyester microspheres via a modified w/o/w double emulsion-solvent extraction protocol with only a partial loss of lytic activity. Loss of lytic activity could be attributed to the exposure of the bacteriophages to the water-dichloromethane interface, with the lyophilization process itself having little effect. The microspheres were engineered to have an appropriate size and density to facilitate inhalation via a dry-powder inhaler and fluorescently labeled bacteriophages were distributed entirely within the internal porous matrix. The release profile showed a burst release phase (55–63% release within 30 min), followed by a sustained release till around 6 h, as appropriate for pulmonary delivery. Despite the poor shelf-life of the formulation, the work is proof-of-concept for the formulation and controlled delivery of bacteriophages, as suitable for the treatment of bacterial lung infections.