Current treatments of bacterial biofilms are limited by the poor penetration of antibiotics through their physical barrier as well as significant off-target toxicity of antibiotics and the induction of antibiotic resistance. Here we report a microneedle patch-mediated treatment for the effective elimination of biofilms by penetrating the biofilm and specifically delivering antibiotics to regions of active growth. We fabricated patches with self-dissolvable microneedles and needle tips loaded with chloramphenicol (CAM)-bearing and gelatinase-sensitive gelatin nanoparticles (CAM@GNPs). During the microneedle patch-mediated treatment, arrays of 225 microneedles simultaneously penetrate the biofilm matrix. Once inside, the microneedles dissolve and uniformly release CAM@GNPs into the surrounding area. In response to the gelatinase produced by the active bacterial community, the CAM@GNPs disassemble and release CAM into these active regions of the biofilm. Moreover, CAM@GNPs exhibited minimal off-target toxicity compared to direct CAM administration, which in turn favors wound healing. Importantly, we found that our microneedle-mediated treatment is more effective in treating Vibrio vulnificus biofilms than drug in free solution. We believe this new treatment strategy can be used to improve the delivery of a wide range of antimicrobial agents to biofilm-contaminated sites.
Keywords: Vibrio vulnificus; antibiotic resistance; biofilm; chloramphenicol; gelatin nanoparticles; microneedle patch; transdermal delivery.