Localized and controlled antibiotic therapy via microneedles: a biomedical approach to antimicrobial resistance

Official URL: https://dx.doi.org/10.1016/j.jddst.2025.107639

The rise of antimicrobial resistance presents a significant global health threat, driven by antibiotic overuse and stagnation in novel drug development. While many effective antibiotics exist, their misuse accelerates the emergence of resistant bacterial strains. Innovative administration strategies are urgently needed to enhance efficacy and minimize resistance. In this study, we present a microneedle-based transdermal delivery platform designed for localized and controlled antibiotic release. Using Escherichia coli and Staphylococcus aureus 494 as model organisms, we evaluated the delivery of clinically relevant concentrations of ampicillin, ciprofloxacin, and kanamycin via polymeric microneedle arrays fabricated using a two-layer micromolding process. Two distinct microneedle geometries were assessed for mechanical integrity through compression and bending tests, as well as in vitro skin penetration studies. Drug release profiles and diffusion kinetics were characterized using dissolution assays and computational modeling. Antimicrobial efficacy was evaluated through time-kill assays, colony-forming unit counts, agar diffusion, and real-time inhibition studies on mature bacterial biofilms. Results show that the microneedles exhibit strong mechanical performance, rapid dissolution, and effective bacterial inhibition. This study highlights the potential of microneedle-based antibiotic delivery as a minimally invasive, spatially targeted therapeutic strategy. By enabling controlled release directly at the infection site, this platform offers a promising solution for improving treatment outcomes of localized infections while reducing the risk of resistance.