The eradication of biofilm for therapy of bacterial infected chronic wound based on pH-responsive micelle of antimicrobial peptide derived biodegradable microneedle patch

Chronic wound caused by bacterial biofilm infection is difficult to heal and has been regard as a medical challenge. Herein, a biodegradable drug-loaded microneedle (MN) patch is designed for biofilm eradication and chronic wound repair. The microneedle system is loaded with micelle ([email protected]) formed by the self-assembly of pH-responsive tri-block polymer (DMA-PEI-PLGA, DPP) and Ce6-coupled antimicrobial peptide (AMP-Ce6, AC), the micelle is about 68 nm in size and can release the DMA group and present positive charge in an acidic environment, thereby significantly improving the specific targeting ability of the antimicrobial peptide to bacteria. In vitro experiment shows that the MIC90 value of [email protected] against S. aureus under laser irradiation is less than 5 μM and can inhibit 90% of biofilm formation. In vivo experiment shows that the MNs are basically degraded after 10 min of skin insertion, and the MN patch loaded with [email protected] is applied to the wound of S. aureus biofilm-infected diabetic mice and irradiated with laser, showing excellent antibacterial peptide and photodynamic synergistic antimicrobial effect, which completely heals the wound within 15 d and achieved synergistic biofilm eradication and subsequent cascade activation of wound healing. Both in vitro and in vivo experiments confirm the biosafety of the microneedle system. This microneedle-assisted antimicrobial therapy provides a highly effective strategy for the treatment of chronic wound with biofilm-associated infection.