Properties of water molecules at the interface between contrast agents (CAs) for magnetic resonance imaging and macromolecules could have a valuable impact on the effectiveness of metal chelates. Recent studies, indeed, demonstrated that polymer architectures could influence CAs' relaxivity by modifying the correlation times of the metal chelate. However, an understanding of the physico-chemical properties of polymer/CA systems is necessary to improve the efficiency of clinically used CAs, still exhibiting low relaxivity. In this context, we investigate the impact of hyaluronic acid (HA) hydrogels on the relaxometric properties of Gd-DTPA, a clinically used CA, to understand better the determining role of the water, which is crucial for both the relaxation enhancement and the polymer conformation. To this aim, water self-diffusion coefficients, thermodynamic interactions and relaxometric properties of HA/Gd-DTPA solutions are studied through time-domain NMR relaxometry and isothermal titration calorimetry. We observed that the presence of Gd-DTPA could alter the polymer conformation and the behaviour of water molecules at the HA/Gd-DTPA interface, thus modulating the relaxivity of the system. In conclusion, the tunability of hydrogel structures could be exploited to improve magnetic properties of metal chelates, inspiring the development of new CAs as well as metallopolymer complexes with applications as sensors and memory devices.
Keywords: contrast agents; hydrogels; magnetic resonance imaging; relaxivity; water interface.