Sanguinarine hydrogel accelerates wound healing in Staphylococcus pseudintermedius infections by suppressing biofilm formation

AIMS: Skin and ear infections are common in small animals, primarily caused by the opportunistic pathogen Staphylococcus pseudintermedius. Staphylococcus pseudintermedius biofilms are associated with poor prognosis, and rising antibiotic resistance threatens public health, making the development of new antibacterial agents imperative. Sanguinarine (SAN) is a plant-derived alkaloid with a wide range of pharmacological activities, including antibacterial, anti-inflammatory, and antitumour effects. The antibacterial potential of SAN against S. pseudintermedius merits further investigation. METHODS AND RESULTS: The minimum inhibitory concentration and minimum bactericidal concentration of SAN hydrogel against clinically isolated S. pseudintermedius were determined as 1.25 and 5 mg mL-1, respectively. Phenol-sulfuric acid and XTT assays demonstrated that SAN hydrogel significantly delayed biofilm formation (P < 0.05) by suppressing exopolysaccharide synthesis and biofilm metabolic activity. Live/dead fluorescent staining and scanning electron microscopy (SEM) confirmed its potent disruptive effects on mature biofilms, inducing bacterial lysis and death, while reducing biofilm thickness and extracellular matrix. In a murine skin infection model, SAN hydrogel (2.5/5 mg mL-1) exhibited significant antibacterial efficacy (P < 0.001), accelerated wound healing, and reduced bacterial load (P < 0.001) and IL-6 levels (P < 0.0001) in skin tissues. No significant hepatorenal toxicity was observed within the tested concentration range. CONCLUSION: The SAN hydrogel demonstrates antimicrobial and bactericidal activities against S. pseudintermedius, effectively suppressing biofilm formation and holding promise as a therapeutic candidate for skin infections caused by this pathogen.