pH-responsive nanocellulose gel based on covalent immobilization and physical adsorption for drug controlled release

The development of drug delivery systems (DDS) aims to enhance therapeutic efficacy and reduce side effects, and hydrogels derived from natural polymers have emerged as promising drug carriers due to their excellent biocompatibility and stimuli-responsive properties. Aldehyde cellulose is a highly reactive cellulose derivative, and the aldehyde groups in its molecules can be used for cross-linking and covalent immobilization of drugs. In this study, TEMPO-oxidized cellulose nanofibers were re-oxidized with periodate, and self-crosslinked dialdehyde cellulose nanofiber gels (DACNFgel) were prepared via aldol condensation reaction. Using sulfathiazole (STZ) and pyrazinamide (PZA) as model drugs, their loading efficiency, release behavior, and release kinetics under different pH conditions were systematically investigated. The results showed that DACNFgel possesses tailorable pore structure and significant pH-dependent swelling behavior; among them, STZ can be covalently immobilized through Schiff base reaction and exhibits pH-sensitive sustained-release characteristics, while the release of PZA is mainly controlled by diffusion processes. In vitro cytotoxicity experiments further confirmed that the gel has good biocompatibility.