Low-solid content cellulose nanofiber/mixed-linkage glucan hydrogels for drug delivery and nanoparticle encapsulation

It is well established that polymer concentration significantly influences drug diffusion. However, achieving mechanically stable networks at low solid content while maintaining sustained and controlled release remains challenging. In this work, we prepared hydrogels composed of TEMPO-oxidized cellulose nanofibers (TCNF) and mixed-linkage β-glucan (MLG) at total solid contents of 0.4% (w/w). Rheological characterization confirmed solid-like viscoelastic behavior, while FTIR, WAXS, and SEM analyses supported the formation of a physically crosslinked nanofibrillar network with a highly porous structure. Drug release studies revealed sustained release behavior governed by molecular size and charge. Compounds with lower molecular weight (4 kDa FITC-dextrans) or negative charge (ketoprofen) exhibited rapid release, reaching cumulative release rates of over 90% within 6-8 h. In contrast, higher molecular weight compounds (40 kDa FITC-dextrans) or positively charged molecules (nadolol) showed slower release profiles, with approximately 70% cumulative release after 24 h. Furthermore, the TCNF/MLG hydrogels exhibited strong retention of liposomal nanocarriers and enabled externally triggered release through the incorporation of light-sensitive liposomes, with the hydrogel matrix effectively converting rapid liposomal release into a sustained profile. Overall, this study evaluated the ability of TCNF/MLG hydrogels for controlled drug delivery applications and highlighted the potential for developing novel therapeutic strategies.