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.