Two series of pH-sensitive semi-interpenetrating network hydrogels (semi-IPN) based on chitosan (CS) natural polymer and acrylamide (AAm) and/or N-hydroxymethyl acrylamide (HMA) monomers by varying the monomer and CS ratios were synthesized by free radical chain polymerization. 5-Fluorouracil (5-FU), a model anticancer drug, has been added to the feed composition before the polymerization. The characterization of gels indicated that the drug is molecularly dispersed in the polymer matrix. The swelling kinetics of drug-loaded gels have decreased with increased HMA content at 37 degrees C in both distilled water and buffer solutions with a pH of 2.1 or 7.4. Elastic modulus of the gels increased with the increase in HMA content and higher CS concentration enhanced the elastic modulus positively. Moreover, cumulative release percentages of the gels for 5-FU were ca. 10% higher in pH 2.1 than those in pH 7.4 media. It was determined that they can be suitable for the use in both gastric and colon environments. (C) 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41886.