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.
Department of Chemistry, University of Warwick, CV4 7AL, Coventry, UK.
Chongyu
C
Zhu
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Jinxin
J
Zhao
Department of Chemistry, University of Warwick, CV4 7AL, Coventry, UK.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Kristian
K
Kempe
Department of Chemistry, University of Warwick, CV4 7AL, Coventry, UK.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Paul
P
Wilson
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Jiping
J
Wang
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Tony
T
Velkov
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Jian
J
Li
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Thomas P
TP
Davis
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
Michael R
MR
Whittaker
Department of Chemistry, University of Warwick, CV4 7AL, Coventry, UK.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia.
David M
DM
Haddleton
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002056:Burns / Q000150:complications / Q000188:drug therapy*; D003091:Colistin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D055119:Elastic Modulus; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014946:Wound Infection / Q000150:complications / Q000188:drug therapy*
D000890:Anti-Infective Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003091:Colistin
burn wound infections; colistin formulation; superbugs; “on-wound” biodegradable hydrogel