A Hydrogel‐Based Localized Release of Colistin for Antimicrobial Treatment of Burn Wound Infection

There is an urgent unmet medical need for new treatments for wound and burn infections caused by multidrug-resistant (MDR) Gram-negative ‘superbugs’, especially the problematic Pseudomonas aeruginosa. In this work we report the incorporation of colistin, a potent lipopeptide into a self-healable hydrogel (via dynamic imine bond formation) following the chemical reaction between the amine groups present in glycol chitosan and an aldehyde modified poly (ethylene glycol) (PEG). The storage module (G’) of the colistin-loaded hydrogel ranged from 1.3 kPa to 5.3 kPa by varying the amount of the cross-linker and colistin loading providing different options for topical wound healing. The majority of the colistin is released from the hydrogel within 24 h and remains active as demonstrated by both antibacterial in vitro disk diffusion and time-kill assays. Moreover and pleasingly, the colistin-loaded hydrogel performed almost equally well as native colistin against both the colistin-sensitive and also colistin-resistant P. aeruginosa strain in the in vivo animal 'burn' infection model despite exhibiting a slower killing profile in vitro. Based on this antibiotic performance along with the biodegradability of the product, we believe the colistin-loaded hydrogel to be a potential localized wound-healing formulation to treat burn wounds against microbial infection.