On-demand radiofrequency-controlled drug release from microcapsule depot in ex vivo tissue model

Passive antibiotic release from implanted depot systems often leads to sub-therapeutic dosing, which in some cases may increase the risk of bacterial resistance. Addressing this limitation requires precise, controllable dosing strategies that do not rely on additional surgical interventions. To this end, this work presents a core-shell depot microcapsule system that enables externally controlled, on-demand antibiotic release using radiofrequency (RF) heating. The microcapsules (d ≈ 500 µm) consist of a norfloxacin-loaded wax solid core and a dually crosslinked methacrylated alginate shell containing superparamagnetic iron oxide nanoparticles (SPIONs). RF-induced heating of the SPIONs triggers the melting of the wax core, initiating drug release only when required, enabling precise repeated delivery up to 10 times. The dual-crosslinked shell ensures structural integrity, maintaining prolonged stability under physiological conditions. Mathematical and experimental models confirm the thermal safety of the process. Furthermore, antibacterial efficacy was validated on Escherichia coli-coated agar plates and in ex vivo animal tissue model, showing significant bactericidal effects in vitro. The findings highlight a promising approach for targeted, responsive antibacterial treatment while minimizing the risks of resistance development.