Chitosan-Based Transdermal Microneedles for Synergistic Sono-Photodynamic Antibacterial Therapy

Bacterial wound infections are often complicated by biofilm formation, which leads to persistent inflammation and multidrug resistance, severely impeding the healing process. Conventional antibiotic therapies are challenged by both overuse and rising antimicrobial resistance. To address this, we designed and fabricated a dual-mode responsive delivery system (C_SO_AC@MN) based on chitosan (CS) and oleanolic acid (OA) composite microneedles for synergistic sono-photodynamic therapy (SPDT). This system employs chlorin e6 (Ce6), which exhibits both photodynamic and sonodynamic activities, as the core antibacterial component. It utilizes the self-assembly properties of OA to form nanoparticles for Ce6 encapsulation, and reinforces the microneedle mechanical strength through composite formation with CS, enabling efficient transdermal delivery. In vitro experiments demonstrated that under combined laser and ultrasound irradiation, the system exhibited strong antibacterial activity against both standard strains (Staphylococcus aureus and Escherichia coli) and a clinically relevant drug-resistant strain and effectively disrupted pre-formed biofilms. The antibacterial effect is attributed to the reactive oxygen species generated during synergistic SPDT. Cytocompatibility assays confirmed good biocompatibility with normal fibroblast cells at effective antibacterial concentrations. This study presents an integrated strategy combining transdermal microneedles with SPDT to combat biofilm-associated infections, showing promising potential for clinical translation.