Biofilm-driven infections represent a critical barrier to effective antimicrobial therapy, contributing significantly to the global burden of antibiotic resistance. Overcoming the limited biofilm penetration, rapid drug clearance, and suboptimal local antibiotic concentrations associated with conventional formulations remains a key therapeutic challenge. In this context, cefuroxime axetil-loaded polymeric nanoparticles based on Eudragit RS100 and RL100 were designed to enhance antibacterial and antibiofilm activity. Polymeric nanoparticle systems offer several advantages, including improved drug stability, enhanced penetration into the biofilm matrix, controlled and sustained drug release, and increased local drug concentration at the site of infection. Antibacterial activity was evaluated against clinically relevant biofilm-forming pathogens (Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 35218), revealing minimum inhibitory concentration (MIC) values ranging from 500 to 15.62 μg/mL. Importantly, the nanoparticulate system demonstrated pronounced antibiofilm efficacy across all tested concentrations. At 500 μg/mL, biofilm inhibition exceeded ≥94±1.48%, indicating near-complete suppression of biofilm formation. Remarkably, substantial inhibition ≥75±1.00% was retained even at the lowest concentration tested (15.62 μg/mL), underscoring the robustness of the formulation. The enhanced antibiofilm activity is likely driven by improved antibiotic diffusion into the biofilm matrix combined with sustained drug release characteristics of the Eudragit polymers, enabling prolonged antimicrobial exposure. Collectively, these findings position Eudragit-based cefuroxime axetil nanoparticles as a robust and promising platform to combat biofilm-associated infections and antimicrobial resistance. This approach highlights the potential of nanoparticle-mediated antibiotic delivery systems for next-generation therapeutic strategies targeting persistent infections.

This study was supported by Anadolu University Scientific Research Projects Commission under the grant no: YTT-2025-3144.