Work

Investigating the role of excipients in mitigating surface adsorption, aggregation and structural degradation in liquid phage formulations

Year: 2026

Type: article

Abstract: The race to produce therapeutically acceptable phages is driven by their rapid loss of infectivity, placing strain on laboratories, healthcare infrastructure and patients. Enhancing product shelf-life will alleviate this barrier to their upscaling and clinical application. We systematically investigated the physicochemical drivers of phage instability using the myovirus, Pae7, under clinically relevant conditions: temperature (4–37 °C), storage materials, NaCl salt and preparation purity. We show that phage instability is not primarily impacted by storage temperature (4–37 °C). Rather, virions adsorbed to container surfaces as a major contributor to titre loss, with borosilicate vials preserving infectivity more effectively than Eppendorf tubes, particularly in 0.9% NaCl solution. Loss of infectivity also occurred concurrently with changes to native state surface charge, structural integrity, aggregation and fragmentation. Notably, crude lysates retained infectivity; meanwhile, purified, patient-grade samples experienced substantial titre loss. These findings indicate that phages behave like colloidal particles and proteins, which directed stabilisation strategies. We characterised phage-excipient interactions and demonstrated the steric stabilisation of patient-grade phages with the biocompatible surfactant, Tween-20, and Reversible Addition-Fragmentation chain Transfer (RAFT) polymers, poly-oligo-(ethylene glycol methyl ether acrylate)- block -poly(3-vinyl-benzaldehyde) (POEGA- b -PVBA) and POEGA as previously unreported excipients, resulting in the maintenance of their infectivity over 56 days. This work has significantly furthered insights into phage destabilising phenomena to establish a rational approach to formulating shelf-stable therapeutic phages.

Source: npj Viruses

DOI: 10.1038/s44298-026-00233-1

Authors: Eleni Siafakas, Hien T. T. Duong, Jonathan R. Iredell

Institutions: The University of Sydney, Westmead Institute for Medical Research, Westmead Hospital, Western Sydney Local Health District

Language: English

Topic: Bacteriophages and microbial interactions

Subfield: Ecology

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,790