New biodegradable pH-responsive hydrogel beads based on chemically modified chitosan and sodium alginate were prepared and characterized for the controlled release study of protein drugs in the small intestine. The ionotropic gelation reaction was carried out under mild aqueous conditions, which should be appropriate for the retention of the biological activity of an uploaded protein drug. The equilibrium swelling studies were carried out for the hydrogel beads at 37 degrees C in simulated gastric (SGF) and simulated intestinal (SIF) fluids. Bovine serum albumin (BSA), a model for protein drugs was entrapped in the hydrogels and the in vitro drug release profiles were established at 37 degrees C in SGF and SIR The preliminary investigation of the hydrogel beads prepared in this study showed high entrapment efficiency (up to 97%) and promising release profiles of BSA. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 115: 2828-2837, 2010