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Deferiprone-Gallium-Protoporphyrin Chitogel Decreases <i>Pseudomonas aeruginosa</i> Biofilm Infection without Impairing Wound Healing
oleh: Tahlia L. Kennewell, Hanif Haidari, Suzanne Mashtoub, Gordon S. Howarth, Catherine Bennett, Clare M. Cooksley, Peter John Wormald, Allison J. Cowin, Sarah Vreugde, Zlatko Kopecki
Format: | Article |
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Diterbitkan: | MDPI AG 2024-02-01 |
Deskripsi
<i>Pseudomonas aeruginosa</i> is one of the most common pathogens encountered in clinical wound infections. Clinical studies have shown that <i>P. aeruginosa</i> infection results in a larger wound area, inhibiting healing, and a high prevalence of antimicrobial resistance. Hydroxypyridinone-derived iron chelator Deferiprone (Def) and heme analogue Gallium-Protoporphyrin (GaPP) in a chitosan-dextran hydrogel (Chitogel) have previously been demonstrated to be effective against PAO1 and clinical isolates of <i>P. aeruginosa</i> in vitro. Moreover, this combination of these two agents has been shown to improve sinus surgery outcomes by quickly reducing bleeding and preventing adhesions. In this study, the efficacy of Def-GaPP Chitogel was investigated in a <i>P. aeruginosa</i> biofilm-infected wound murine model over 6 days. Two concentrations of Def-GaPP Chitogel were investigated: Def-GaPP high dose (10 mM Def + 500 µg/mL GaPP) and Def-GaPP low dose (5 mM Def + 200 µg/mL GaPP). The high-dose Def-GaPP treatment reduced bacterial burden in vivo from day 2, without delaying wound closure. Additionally, Def-GaPP treatment decreased wound inflammation, as demonstrated by reduced neutrophil infiltration and increased anti-inflammatory M2 macrophage presence within the wound bed to drive wound healing progression. Def-GaPP Chitogel treatment shows promising potential in reducing <i>P. aeruginosa</i> cutaneous infection with positive effects observed in the progression of wound healing.