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February 28, 2026International Journal of Antimicrobial Agents3 citationsOpen Access

Formulating and stabilising therapeutic phages: A review

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ESEleni SiafakasHDHien T.T. DuongJIJonathan R. Iredell

Key Points

  • The review aims to analyze the factors influencing the stability and shelf-life of therapeutic phages, highlighting knowledge gaps for future studies.
  • Reviewed literature on therapeutic phage stability and formulation techniques.
  • Discussed influences of container materials, pH, temperature, and ionic interactions on phage viability.
  • Identified suitable excipients including polymers and surfactants for enhancing stability.
  • Therapeutic phage stability is highly dependent on specific conditions and materials used during storage.
  • Loss of infectivity is linked to surface adsorption and aggregation, affected by pH and temperature extremes.
  • Identified non-ionic surfactants as the most effective excipients for extending phage shelf-life.

Abstract

• Therapeutic phage stability in storage conditions appears to be phage dependent but is underpinned by maintaining colloidal stability and protein structural and functional integrity. • Loss of infectivity may be attributed to container surface adsorption, aggregation phenomena, extreme pHs, osmotic shock and accelerated by extreme temperatures. • Electrolytes can reversibly induce phage aggregation, and further work should be conducted into the interactions between ions and phage protein conformation as well as “salting in” and “salting out” behaviours. • The most suitable excipients (polymers and surfactants) to extend shelf-life in liquid preparations and semi-solid formulations appear to be non-ionic in composition. Bacteriophages (phages) have been revitalised as a promising alternative option to combat antibiotic resistant bacteria. However, the ability to upscale and commercialise this therapy is currently limited by the poor shelf-stability of therapeutic preparations. Phage therapy has been ongoing for a century yet a standardised approach to formulating therapeutic phages is currently lacking due to the diverse chemical landscape of these viruses and the different storage methods reported. With consideration of protein and biotherapeutic literature, this review examines the evidence surrounding the effects of container materials, buffers and media, salt 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. Thus, the aim of this review is to discuss current findings, identify knowledge gaps and inform the direction of future stabilisation studies.

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Cite This Study

Siafakas et al. (2026) studied this question.

synapsesocial.com/papers/69a286240a974eb0d3c00e1ahttps://doi.org/10.1016/j.ijantimicag.2026.107759
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