Methods for Delivery of Bacteriophage to Lung for Reducing Bacterial Colonization
This technology includes methods for the delivery of active bacteriophages or other agents to the lung, with the goal of reducing bacterial colonization and improving clinical outcomes. This is accomplished by encapsulating, immobilizing, or otherwise incorporating bacteriophages to polymer particles in the micro- to nano-scale size range in order to target their delivery to specific lung regions. The current example of this involves poly(lactic-co-glycolic) acid (PLGA) particles conjugated to phages that kill Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Bacteriophages are viruses that infect and kill specific strains of bacteria, are self-replicating and self-limiting, are able to kill multi-drug-resistant bacteria, and are able to penetrate infected tissues. Evidence exists that they can be safely administered therapeutically to humans. We have a collection of more than 30 phages infecting Pseudomonas aeruginosa, and have determined that at least some of them can kill P. aeruginosa isolated from the lungs of cystic fibrosis patients. PLGA is an FDA-approved biodegradable synthetic polymer that is well-suited for pulmonary delivery.
- Improved delivery of novel therapeutics to the small airways of the lung by controlling particle properties
- Use of therapeutic agents that are able to kill multi-drug resistant pathogenic bacteria that are directly responsible for patient morbidity and mortality
- This invention addresses technological and therapeutic gaps, specifically the shortage of antibacterial agents available to combat chronic lung infections that are refractory to current drug treatments, and the current difficulties in targeting therapeutic agents to specific areas of the lung, wholly or partly independent of the size of the therapeutic agent itself.
- This technology should be extendable to antibacterial agents other than bacteriophages.
- A major strength of using these particles as delivery vehicles is the ability to incorporate or co-deliver other molecules that may enhance the efficacy of bacteriophages or act independently.
- The current example of the invention uses particles that follow a two-phase decay process, which potentially allows for delayed release of small molecules as the particle decays.