A dissolving microneedle patch for Antibiotic/Enzymolysis/Photothermal triple therapy against bacteria and their biofilms

Abstract

The biofilms present in wounds are difficult to eliminate due to the compact barrier formed by extracellular polymeric substances (EPS). Herein, we have designed a dissolvable microneedle patch that destroys the structure of EPS matrix by enzymolysis and kills the exposed bacteria by the combination of photothermal- and chemo- therapy. The microneedles can destroy the physical barrier of biofilms and release α-amylase to degrade the extracellular polysaccharide of EPS, making the bacteria susceptible to antimicrobial therapies. Furthermore, the levofloxacin-loaded polydopamine nanoparticles (PDA@Levo) encapsulated in microneedles can achieve both antibiotic and mild photothermal therapy (PTT, 50 °C) under 808 nm laser irradiation to synergistically eradicate bacteria. The combined use of enzymolysis, antibiotics and PTT therapy effectively removed the biofilms. The in vitro experiments showed the biomass of biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa was reduced to 12.6% and 31.3%, respectively. In vivo, the α-amylase-PDA@Levo microneedle (MN) could remove biofilms from infected wounds and kill exposed bacteria, thereby reducing inflammation and further facilitating the wound healing process, while the mild PTT did not cause damage to normal tissues. We believe that this new multimodal therapy microneedle patch holds great potential in combating bacterial biofilms that are associated with wound infections.