pH-Responsive Cellulose/Silk/Fe₃O₄ Hydrogel Microbeads Designed for Biomedical Applications

In this study, cellulose/Fe₃O₄ hydrogel microbeads were prepared through the sol-gel transition of a solvent-in-oil emulsion using various cellulose-dissolving solvents and soybean oil without surfactants. Particularly, 40% tetrabutylammonium hydroxide (TBAH) and 40% tetrabutylphosphonium hydroxide (TBPH) dissolved cellulose at room temperature and effectively dispersed Fe₃O₄, forming cellulose/Fe₃O₄ microbeads with an average diameter of ~15 µm. Additionally, these solvents co-dissolved cellulose and silk, allowing for the manufacture of cellulose/silk/Fe₃O₄ hydrogel microbeads with altered surface characteristics. Owing to the negatively charged surface characteristics, the adsorption capacity of the cellulose/silk/Fe₃O₄ microbeads for the cationic dye crystal violet was >10 times higher than that of the cellulose/Fe₃O₄ microbeads. When prepared with TBAH, the initial adsorption rate of bovine serum albumin (BSA) on the cellulose/silk/Fe₃O₄ microbeads was 18.1 times higher than that on the cellulose/Fe₃O₄ microbeads. When preparing TBPH, the equilibrium adsorption capacity of the cellulose/silk/Fe₃O₄ microbeads for BSA (1.6 g/g) was 8.5 times higher than that of the cellulose/Fe₃O₄ microbeads. The pH-dependent BSA release from the cellulose/silk/Fe₃O₄ microbeads prepared with TBPH revealed 6.1-fold slower initial desorption rates and 5.2-fold lower desorption amounts at pH 2.2 than those at pH 7.4. Cytotoxicity tests on the cellulose and cellulose/silk composites regenerated with TBAH and TBPH yielded nontoxic results. Therefore, cellulose/silk/Fe₃O₄ microbeads are considered suitable pH-responsive supports for orally administered protein pharmaceuticals.