Controlled release of entrapped nanoparticles from thermoresponsive hydrogels with tunable network characteristics

The work focuses on how nanoparticles move inside thermoresponsive hydrogels made from PNIPAM, a polymer whose network changes when temperature crosses its lower critical solution temperature. The goal is to understand release kinetics and transport mechanisms to support smart drug delivery design. A mesoscopic model is constructed for rigid nanoparticles entrapped in a cross-linked PNIPAM hydrogel network in water. By changing temperature across the PNIPAM transition, the study examines how network porosity and nanoparticle size influence nanoparticle transport. Results based on mean-squared displacement and van Hove displacement distributions show subdiffusion at both low and high temperatures. In the coil state, nanoparticle diffusion is enhanced by increased kinetic energy and reduced confinement, and it can also be improved by decreasing matrix porosity and nanoparticle size. Above the critical temperature, the network collapses (coil-to-globule transition), trapping nanoparticles in local regions and reducing diffusion by up to two orders of magnitude or stopping diffusion entirely. The findings are presented as design insights for controlled drug release, including the possibility of autonomously switching drug release on/off in response to local environmental changes.