2-Hydroxyethyl methacrylate was copolymerized with acrylamide, N-vinyl-2-pyrrolidone, and n-butyl methacrylate by free-radical solution polymerization with alpha,alpha'-azobisisobutyronitrile as an initiator at 70 +/- 1 degrees C. The average molecular weights and molar compositions of the resultant copolymers were determined with gel permeation chromatography and H-1-NMR spectroscopy data, respectively. Diclofenac or 2-[(2,6-dichlorophenyl)amino]benzene acetic acid, a nonsteroidal anti-inflammatory drug, was chemically attached to the copolymers by transesterification reaction in the presence of N,N'-dicyclohexyl-carbodiimide to give macromolecular prodrugs. All the synthesized polymers were characterized with Fourier transform infrared, H-1-, and C-13-NMR spectroscopy techniques. The polymer-drug conjugates were hydrolyzed in cellophane member dialysis bags containing aqueous buffered solutions (pH 8) at 37 degrees C, and the hydrolysis solutions were detected by UV spectrophotometer at selected intervals. The results showed that the drug could be released by selective hydrolysis of the ester bond from the side chain of the drug moiety. The release profiles of the drug indicated that the hydrolytic behavior of polymeric prodrugs strongly depends on the hydrophilicity of the polymer. The results suggest that the synthesized copolymers could be useful carriers for the release of diclofenac in controlled-release systems. (c) 2007 Wiley Periodicals, Inc.