Effects of storage conditions on the stability of spray dried, inhalable bacteriophage powders

Sharon S Y Leung1, Thaigarajan Parumasivam1, Fiona G Gao1

  • 1Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia.

Insights

Stable inhalable phage powders were developed using spray drying for treating antibiotic-resistant Pseudomonas aeruginosa lung infections. Formulations with at least 40% trehalose maintained phage viability and aerosol performance after 12 months of storage.

Area of Science:

  • Microbiology
  • Pharmaceutical Sciences
  • Biotechnology

Background:

  • Antibiotic-resistant bacteria, particularly Pseudomonas aeruginosa, pose a significant threat in pulmonary infections.
  • Bacteriophages (phages) offer a promising alternative antimicrobial strategy.
  • Developing stable phage formulations for effective pulmonary delivery is crucial.

Purpose of the Study:

  • To develop inhalable phage powders containing phages active against antibiotic-resistant Pseudomonas aeruginosa for pulmonary delivery.
  • To evaluate the stability and aerosol performance of spray-dried phage powders under various storage conditions.

Main Methods:

  • Pseudomonas phage PEV2 was spray-dried into powder matrices containing trehalose, mannitol, and l-leucine.
  • Powders were stored at 4°C under varying relative humidity (0, 22, and 60% RH).
  • Phage stability (titer reduction) and in vitro aerosol performance were assessed over 12 months.

Main Results:

  • Spray drying resulted in minimal phage titer reduction (1.3 log) in formulations with ≥40% trehalose.
  • Powders stored at 0 and 22% RH showed good phage stability over 12 months, except for formulations without trehalose.
  • Storage at 60% RH led to complete loss of viable phages within 3-12 months.
  • Formulations with ≥40% trehalose demonstrated comparable aerosol lung doses (approx. 10^5 pfu).

Conclusions:

  • Spray drying is a viable method for producing stable phage powders for pulmonary delivery.
  • Powder matrices containing ≥40% trehalose ensure good phage preservation and aerosol performance.
  • Low relative humidity storage conditions (0-22% RH) at 4°C are optimal for long-term phage powder stability.