Deferiprone-Gallium-Protoporphyrin Chitogel Decreases Pseudomonas aeruginosa Biofilm Infection without Impairing
Tahlia L Kennewell1, Hanif Haidari1, Suzanne Mashtoub2,3
1Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia.
Abstract:
Pseudomonas aeruginosa is one of the most common pathogens encountered in clinical wound infections. Clinical studies have shown that P. aeruginosa 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 P. aeruginosa 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 P. aeruginosa 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 P. aeruginosa cutaneous infection with positive effects observed in the progression of wound healing.
Insights
Def-GaPP Chitogel effectively combats Pseudomonas aeruginosa wound infections in mice. This treatment reduced bacterial load and inflammation, promoting faster wound healing without delaying closure.
Area of Science:
- Wound Healing and Regenerative Medicine
- Antimicrobial Therapy
- Biomaterials Science
Background:
- Pseudomonas aeruginosa is a common cause of difficult-to-heal wound infections, often exhibiting antimicrobial resistance.
- Iron chelators and heme analogues show in vitro efficacy against P. aeruginosa.
- Chitosan-dextran hydrogel (Chitogel) serves as a drug delivery vehicle.
Purpose of the Study:
- To evaluate the in vivo efficacy of Deferiprone (Def) and Gallium-Protoporphyrin (GaPP) loaded in Chitogel (Def-GaPP Chitogel) against Pseudomonas aeruginosa biofilm-infected wounds.
- To assess the impact of Def-GaPP Chitogel on bacterial burden, wound closure, and inflammatory responses in a murine wound model.
Main Methods:
- A murine model of P. aeruginosa biofilm-infected wounds was established.
- Wounds were treated with two concentrations of Def-GaPP Chitogel (high dose: 10 mM Def + 500 µg/mL GaPP; low dose: 5 mM Def + 200 µg/mL GaPP) over 6 days.
- Bacterial burden, wound closure rate, neutrophil infiltration, and macrophage polarization (M1/M2) were assessed.
Main Results:
- High-dose Def-GaPP Chitogel significantly reduced bacterial burden starting from day 2 post-infection.
- Treatment did not impede wound closure.
- Def-GaPP Chitogel decreased neutrophil infiltration and increased anti-inflammatory M2 macrophage presence, indicating reduced inflammation and promotion of healing.
Conclusions:
- Def-GaPP Chitogel demonstrates significant potential for treating P. aeruginosa cutaneous infections.
- The formulation effectively reduces bacterial load and modulates the inflammatory environment to accelerate wound healing.
