Objective: To formulate pH-sensitive spray dried microspheres loaded with an anti-cancer drug, capecitabine, using hydrolyzed polyacrylamide-grafted-acacia gum (PAAm-g-AG) for colon targeted delivery.Methods: The pH-sensitive PAAm-g-AG was synthesized by free radical polymerization and allowed for alkaline hydrolysis. Results: The obtained microspheres were sphere-shaped and drug encapsulation efficiency was found to be from 76.29% to 97.66%. The dynamic swelling investigation suggested that the PAAm-g-AG attained significant pH-sensitivity property. The in vitro drug release study witnessed that the microspheres prepared with native AG alone were not capable of stopping the drug release within 5 h in stomach and small intestinal pH. But, those microspheres prepared using pH-sensitive PAAm-g-AG having crosslinked with glutaraldehyde (GA), have released small quantity of drug within 5 h, and highest amount of drug was moved to colonic region in a controlled manner up to 24 h. Cross-linking with GA reduced the premature drug release in the pH of stomach and small intestine and also assured most of the drug released in colonic region. We observed an abrupt increase in drug release in the presence of rat caecal contents due to the action of colonic bacteria on PAAm-g-AG polymer.