In this study, we investigated some hydrogels based on natural, biodegradable, and biocompatible polysaccharides and cellulose, as sustained release carriers and evaluated their controlled drug release. The crosslinking of bromoacetylated cellulose with various aliphatic and aromatic diamines, such as ethylene diamine, hexamethylene diamine, and paraphenylene diamine, were carried out in N,N-dimethylformamide in the presence of triethylamine as a base. On the other hand, the synthesized hydrogels were characterized with Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and CHN elemental analysis. Also, the equilibrium swelling behavior of the hydrogels in water was calculated, and this indicated their sustained expansion. The loading of ceftizoxime antibiotic was carried out on the prepared hydrogels, and the in vitro and drug-release behaviors were investigated in three different media (HCl solution at pH 3 and bicarbonate buffer solutions at pH 6 and 8). Finally, the release profiles of ceftizoxime from the hydrogels and their loading capacities were determined by ultraviolet-visible absorption measurements at λmax 295 nm. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42568. © 2015 Wiley Periodicals, Inc.