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 Gram-negative "superbugs," especially the problematic Pseudomonas aeruginosa. In this work, 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), is reported. The storage module (G') of the colistin-loaded hydrogel ranges from 1.3 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 performs 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, it is believed the colistin-loaded hydrogel to be a potential localized wound-healing formulation to treat burn wounds against microbial infection.