Formulating and stabilising therapeutic phages: A review

Bacteriophages (phages) have been revitalised as a promising alternative option to combatantibiotic resistant bacteria. However, the ability to upscale and commercialise this therapy is currently limitedby the poor shelf-stability of therapeutic preparations. Phage therapy has been ongoing for a century yet astandardised approach to formulating therapeutic phages is currently lacking due to the diverse chemicallandscape of these viruses and the different storage methods reported. The aim of this review is to discusscurrent findings, identify knowledge gaps, and inform the direction of future stabilisation studies.

With consideration of protein and biotherapeutic literature, this review examines the evidence surrounding the effects of container materials, buffers and media, salts and ions, pH, temperature, polymers, surfactants and semi-solid formulations on the shelf stability of phages.

Loss of viability appears to be phage dependent but can be attributed to surface adsorption, colloidal instability, aggregation phenomena, and compromises to structural integrity and function.

Key future research areas should investigate the interplay of containers, ions, pH, and temperature on phage structure, function, and aggregation phenomena. Preservation strategies should look to non-ionic, biocompatible polymers and surfactants as excipients for clinical application.