Hyaluronic acid-based hydrogels: Drug diffusion investigated by HR-MAS NMR and release kinetics

Hydrogels based on hyaluronic acid (HA) and agarose-carbomer (AC) raised an increasing interest as drug de-livery systems. The complex architecture of the polymer network, such as mesh size, HA molecular weight and drug-polymer non covalent interactions across the 3D polymer matrix strongly influence the release capability/ profile of these materials. In this study, AC-HA hydrogels with different mesh sizes have been prepared and characterised. High Resolution Magic Angle Spinning (HR-MAS) NMR spectroscopy has been used to investigate the motion of two drugs, such as ethosuximide (neutral molecule) and sodium salicylate (net negative charge) within the AC and AC-HA hydrogel networks. Analysis of the experimental data provides evidence of super -diffusive motion for all formulations containing sodium salicylate, while ethosuximide molecules undergo un-restricted diffusion within the gel matrix. We further speculate that the superdiffusive motion, observed at the nanoscale, can be responsible for the faster release of sodium salicylate from all hydrogel formulations.