A. Viteri et al. Tailoring drug release from skin-like chitosan-agarose biopolymer hydrogels containing Fe3O4 nanoparticles using magnetic fields. Chemical Engineering Journal

A. Viteri, M. Espanol, M.P. Ginebra, J. García-Torres. Tailoring drug release from skin-like chitosan-agarose biopolymer hydrogels containing Fe3O4 nanoparticles using magnetic fields. Chemical Engineering Journal, Volume 517, 1 August 2025, 164214. OPEN ACCESS.

doi: doi.org/10.1016/j.cej.2025.164214

Abstract

Controlled drug release is essential in personalized medicine, requiring innovative materials and strategies. Magnetically responsive hydrogels are promising candidates due to their biocompatibility, softness, flexibility, and ability to enable remote, non-invasive drug modulation using magnetic fields. However, biopolymer-based magnetic hydrogels often suffer from poor mechanical properties, mismatch with native tissue mechanics, and complex synthesis and magnetic setups. Here, we present a novel interpenetrated double biopolymer network of chitosan and agarose incorporating Fe3O4 nanoparticles and vancomycin as a model antibiotic. This system overcomes prior limitations by combining mechanical robustness with tunable magnetic responsiveness. The hydrogel was synthesized through an easy, eco-friendly, and scalable method with magnetite contents of 10, 20, and 30 wt.%, allowing tuning of physicochemical (swelling, contact angle, biodegradability), mechanical, and magnetic properties. Biocompatibility was confirmed via human foreskin fibroblast cultures, which exhibited well-spread, interconnected cells, indicating a favorable microenvironment for adhesion and growth. Moreover, hydrogel composition also allowed modulating drug release kinetics. Thus, we observed that under the influence of a magnetic field, the release of vancomycin from the magnetic hydrogel was lower. This effect was more noticeable when the magnetite content was higher. Mathematical analysis of the release profiles using different models revealed that the main mechanism is dissolution-diffusion. As a proof of concept, the controlled drug release from the magnetic hydrogel was studied over bacteria cultures analysing the inhibition halo. It was confirmed that vancomycin release on the bacteria culture was controlled depending on hydrogel composition and magnetic field strength as different inhibition halos were observed. The developed chitosan/agarose/Fe3O4 hydrogel can pave the way to a new generation of magnetic hydrogels as drug delivery systems with controlled release via magnetic fields.