Characteristics of TEMPO-oxidized cellulose fibril-based hydrogels induced by cationic ions and their properties

Cellulose microfibrils (CMFs) and cellulose nanofibrils (CNFs) were isolated from hardwood pulp by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation, which produced negatively-charged carboxylate groups on their surface. First, these CMFs and CNFs were used to prepare microgels and nanogels, respectively, at different concentrations of cellulose and trivalent Al³⁺ cation by inducing ionic interactions between the negatively charged carboxylates and the metal cation. Then, two other cations (i.e., divalent Ca²⁺ and monovalent H⁺ were employed to understand the structure–property relationship these hydrogels. We characterized their morphology, chemical groups, mechanical properties, surface area, and pore size, and evaluated their drug-release behaviors using theophylline. Compared to the hydrogels prepared from divalent or monovalent cations, both microgel and nanogel prepared from trivalent Al³⁺ showed the highest stiffness and compressive strength, which indicated that they possessed the strongest ionic cross-linking via intra- and inter-fibrillar interactions. With a decrease in the valency of the cation used, the surface area of both hydrogels decreased, while their pore radius and calculated fibril diameter increased, indicating that a higher valency cation produced a hydrogel with higher porosity and a tighter network structure. The nanogel prepared from Al³⁺ also showed the highest swelling ratio and the lowest release of theophylline, while that of microgel was, in contrast, consistent. The low total drug-release behavior in nanogels was attributed to their compact and highly porous structure. The Higuchi model was the best-fit model of drug release kinetics. These results indicate that the characteristics and internal structure of hydrogel has a great impact on its properties and drug-release profile, and that it may be possible to finely tune hydrogel properties and drug release profile by altering the internal structure of hydrogels during its preparation.