Issue 1, 2024

A thermosensitive hydrogel formulation of phage and colistin combination for the management of multidrug-resistant Acinetobacter baumannii wound infections

Abstract

Chronic skin wounds are often associated with multidrug-resistant bacteria, impeding the healing process. Bacteriophage (phage) therapy has been revitalized as a promising strategy to counter the growing concerns of antibiotic resistance. However, phage monotherapy also faces several application drawbacks, such as a narrow host spectrum, the advent of resistant phenotypes and poor stability of phage preparations. Phage–antibiotic synergistic (PAS) combination therapy has recently been suggested as a possible approach to overcome these shortcomings. In the present study, we employed a model PAS combination containing a vB_AbaM-IME-AB2 phage and colistin to develop stable wound dressings of PAS to mitigate infections associated with Acinetobacter baumannii. A set of thermosensitive hydrogels were synthesized with varying amounts of Pluronic® F-127 (PF-127 at 15, 17.5 and 20 w/w%) modified with/without 3 w/w% hydroxypropyl methylcellulose (HPMC). Most hydrogel formulations had a gelation temperature around skin temperature, suitable for topical application. The solidified gels were capable of releasing the encapsulated phage and colistin in a sustained manner to kill bacteria. The highest bactericidal effect was achieved with the formulation containing 17.5% PF-127 and 3% HPMC (F5), which effectively killed bacteria in both planktonic (by 5.66 log) and biofilm (by 3 log) states and inhibited bacterial regrowth. Good storage stability of F5 was also noted with negligible activity loss after 9 months of storage at 4 °C. The ex vivo antibacterial efficacy of the F5 hydrogel formulation was also investigated in a pork skin wound infection model, where it significantly reduced the bacterial burden by 4.65 log. These positive outcomes warrant its further development as a topical PAS-wound dressing.

Graphical abstract: A thermosensitive hydrogel formulation of phage and colistin combination for the management of multidrug-resistant Acinetobacter baumannii wound infections

Article information

Article type
Paper
Submitted
24 8 2023
Accepted
16 10 2023
First published
23 10 2023

Biomater. Sci., 2024,12, 151-163

A thermosensitive hydrogel formulation of phage and colistin combination for the management of multidrug-resistant Acinetobacter baumannii wound infections

S. Mukhopadhyay, K. K. W. To, Y. Liu, C. Bai and S. S. Y. Leung, Biomater. Sci., 2024, 12, 151 DOI: 10.1039/D3BM01383A

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