Codelivering Polymyxin B and Phage Using Thermosensitive Hydrogel for Treating Carbapenem-Resistant Acinetobacter baumannii-Mediated Wound Infections.

The increasing prevalence of wound infections caused by multidrug-resistant Gram-negative bacteria, particularly carbapenem-resistant Acinetobacter baumannii (CRAB), necessitates novel therapeutic strategies to overcome the limitations of single-agent treatments. This study presents a synergistic treatment strategy by co-delivering bacteriophages and polymyxin B loaded within a poloxamer F127-based thermosensitive hydrogel. Sodium hyaluronate (HA) was incorporated to improve the poor viscoelasticity of the pure F127 hydrogel at low temperatures, thereby enabling practical handling without compromising its thermogelling properties. In a mouse model of full-thickness wounds infected with CRAB, the hydrogel-treated group exhibited significantly accelerated wound closure and improved histopathological outcomes compared to those observed in the controls receiving monotherapies or a blank hydrogel. This study establishes a practical and effective co-delivery platform that combines enhanced material properties with a potent synergistic antimicrobial strategy for managing complex resistant wound infections.