Phage cocktail powder for Pseudomonas aeruginosa respiratory infections

Mengyu Li1, Rachel Yoon Kyung Chang1, Yu Lin1

  • 1Advanced Drug Delivery Group, School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

Insights

A novel phage cocktail powder was developed for inhaled therapy, showing stability and effectiveness against multidrug-resistant Pseudomonas aeruginosa. This formulation broadens the antibacterial spectrum and combats bacterial resistance.

Area of Science:

  • Microbiology
  • Pharmaceutical Sciences
  • Biotechnology

Background:

  • Phage therapy offers a promising alternative for treating bacterial infections, particularly those caused by multidrug-resistant (MDR) pathogens.
  • Single-phage formulations may have limitations in host range and can lead to the development of phage-resistant bacteria.
  • Inhaled phage therapy requires stable, inhalable formulations for effective pulmonary delivery.

Purpose of the Study:

  • To develop a stable and inhalable phage cocktail powder for treating pulmonary infections caused by MDR Pseudomonas aeruginosa.
  • To evaluate the viability, particle characteristics, and aerosol performance of the spray-dried phage cocktail.
  • To assess the in vitro efficacy of the phage cocktail against relevant bacterial strains.

Main Methods:

  • A phage cocktail of three Pseudomonas phages (PEV2, PEV1, PEV20) was produced by spray drying with lactose and leucine excipients.
  • Phage viability, powder characteristics (particle size, moisture content), and amorphous/crystalline structure (X-ray diffraction) were analyzed.
  • Aerosolization performance was evaluated using Osmohalers, determining the fine particle fraction (FPF) at different flow rates.

Main Results:

  • The spray-dried phage cocktail powder maintained phage viability with minimal titer reduction.
  • The powder exhibited desirable characteristics, including a small particle size (1.9 µm) and low moisture content (3.5%).
  • The formulation achieved significant fine particle fractions (45.37%–62.69%), indicating good inhalability.

Conclusions:

  • The developed PEV phage cocktail powder is stable, inhalable, and demonstrates in vitro efficacy against MDR P. aeruginosa.
  • This formulation broadens the bactericidal spectrum compared to single-phage approaches.
  • The phage cocktail formulation effectively reduces the emergence of bacterial resistance, enhancing long-term therapeutic potential.