Honokiol-Loaded β-D-Glucan/Chitosan Nanoparticles with Antibacterial and Anti-Inflammatory Activities for Promoting MRSA-Infected Wound Healing

Background: Methicillin-resistant Staphylococcus aureus (MRSA) wound infections are a major clinical concern due to their high prevalence and the growing risk of antimicrobial resistance. Therefore, it is imperative to develop safe and effective therapeutic strategies. Methods: Herein, we fabricated a novel antibiotic-free nanodrug delivery system (HNK/DG-COS NPs) by loading honokiol (HNK), a hydrophobic natural antimicrobial agent, onto a dual-polysaccharide carrier composed of chitosan (COS) and β-D-glucan (DG), for the treatment of MRSA-infected wounds. COS endows the nanoparticles with synergistic antibacterial activity together with HNK, while DG improves their anti-inflammatory and tissue repair capacities. The physicochemical characteristics of nanoparticles, as well as their in vitro antibacterial and anti-inflammatory activities, were systematically evaluated. Furthermore, an MRSA-infected wound model was constructed to verify their therapeutic efficacy. Results: HNK/DG-COS NPs exhibited a spherical morphology with a uniform particle size of approximately 200 nm. In vitro experiments have shown that HNK/DG-COS NPs can significantly kill MRSA and inhibit biofilm formation. Scanning electron microscopy further revealed that the nanoparticles exerted antibacterial effects by disrupting the integrity of bacterial cell membranes. In LPS-stimulated RAW264.7 macrophages, treatment with HNK/DG-COS NPs significantly mitigated pro-inflammatory cytokine levels. Cell migration assays confirmed that nanoparticles effectively enhanced L929 cell migration. In vivo, treatment with HNK/DG-COS NPs significantly accelerated MRSA-infected wound healing in mice, mitigated inflammatory damage, stimulated collagen production and repaired damaged tissues. Conclusions: HNK/DG-COS NPs represent a promising antibiotic-free candidate for intervention against early-stage MRSA-infected wounds.