Deferiprone and Gallium-Protoporphyrin Chitogel as an antimicrobial treatment: Preclinical studies demonstrating antimicrobial activity for S. aureus infected cutaneous wounds

• Published in: International journal of biological macromolecules Vol. 276; no. Pt 1; p. 133874
• Main Authors: Kennewell, T.L., Haidari, H., Mashtoub, S., Howarth, G.S., Wormald, P.J., Cowin, A.J., Vreugde, S., Kopecki, Z.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2024
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antibiotic-resistant bacteria; Biofilms; Biofilms - drug effects; Chitosan - chemistry; Chitosan - pharmacology; Deferiprone - chemistry; Deferiprone - pharmacology; Deferiprone - therapeutic use; Drug delivery; Gallium - chemistry; Gallium - pharmacology; Hydrogel; Hydrogels - chemistry; Mice; Microbial Sensitivity Tests; Protoporphyrins - chemistry; Protoporphyrins - pharmacology; Pyridones - chemistry; Pyridones - pharmacology; Pyridones - therapeutic use; Skin - drug effects; Skin - microbiology; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus aureus - drug effects; Wound Healing - drug effects; Wound infection; Wound Infection - drug therapy; Wound Infection - microbiology; Wound infection; Drug delivery; Biofilms; Antibiotic-resistant bacteria; Hydrogel
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.133874

Staphylococcus aureus (S. aureus) is one of the most common wound pathogens with increased resistance towards currently available antimicrobials. S. aureus biofilms lead to increase wound chronicity and delayed healing. Chitosan-dextran hydrogel (Chitogel) loaded with the hydroxypyridinone-derived iron chelator Deferiprone (Def) and the heme analogue Gallium-Protoporphyrin (GaPP) have previously been shown to have antimicrobial effects in clinical sinusitis. In this study, the efficacy of Chitogel loaded with Def, GaPP and a combination of Def and GaPP, were investigated in an S. aureus biofilm infected wound murine model over 10 days of treatment. Bacterial wound burden was monitored daily showing a significant decrease in bacterial bioburden on days 6 and 8 when treated with Def-GaPP Chitogel (log10 1.0 and 1.2 reduction vs control, respectively). The current study demonstrates that the combination of Def-GaPP delivered in a Chitogel in vivo is not only effective in reducing S. aureus biofilm infection, but also improves cutaneous healing via effects on reduced inflammation, promotion of anti-inflammatory macrophage phenotype and marked early collagen deposition in the wound bed. This delivery platform presents a promising alternative non-toxic, antibacterial, wound-promoting treatment as a novel approach for the management of S. aureus wound infections that warrants further clinical investigation. [Display omitted] •Chitogel delivery platform for Def-GaPP treatment warrants further investigation for management of wound infection.•Def-GaPP Chitogel shows strong antimicrobial properties against S. aureus wound biofilms.•Def-GaPP Chitogel treatment of infected wounds promotes healing, reduces inflammation, and improves collagen deposition.