TEMPO-Nanocellulose/Ca2+ Hydrogels: Ibuprofen Drug Diffusion and In Vitro Cytocompatibility
Andrea Fiorati, Nicola Contessi Negrini, Elena Baschenis, Lina Altomare, Silvia Farè, Alberto Giacometti Schieroni, Daniele Piovani, Raniero Mendichi, Mónica Ferro, Franca Castiglione, Andrea Mele, Carlo Punta, Lucio Melone
Abstract
Stable hydrogels with tunable rheological properties were prepared by adding Ca2+ ions to aqueous dispersions of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-oxidized and ultra-sonicated cellulose nanofibers (TOUS-CNFs). The gelation occurred by interaction among polyvalent cations and the carboxylic units introduced on TOUS-CNFs during the oxidation process. Both dynamic viscosity values and pseudoplastic rheological behaviour increased by increasing the Ca2+ concentration, confirming the cross-linking action of the bivalent cation. The hydrogels were proved to be suitable controlled release systems by measuring the diffusion coefficient of a drug model (ibuprofen, IB) by high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy. IB was used both as free molecule and as a 1:1 pre-formed complex with β-cyclodextrin (IB/β-CD), showing in this latter case a lower diffusion coefficient. Finally, the cytocompatibility of the TOUS-CNFs/Ca2+ hydrogels was demonstrated in vitro by indirect and direct tests conducted on a L929 murine fibroblast cell line, achieving a percentage number of viable cells after 7 days higher than 70%.