Dopamine (DA) was covalently linked via succinic anhydride spacers to poly(ethylene glycol)s (PEGs) with average molecular weights of 4000 (PEG4000), 6000 (PEG6000), and 10,000 (PEG10000). The chemical modification of the PEGs was conducted by a two-step protocol: (1) the preparation of PEG having carboxylic end groups and (2) the synthesis of PEG4000-DA, PEG6000-DA, and PEG10000-DA. The controlled drug-release studies were performed in pH 1.1, 7.4, and 9.0 buffer solutions, The results demonstrate that under the same conditions, the rate of hydrolysis for PEG10000-DA was the slowest among three prodrugs, and a greater amount of DA could be detected being released from the prodrug matrices in the presence of alpha-chymotrypsin in a buffer solution with pH 8.0. Also, these novel prodrugs could slowly release the active drug molecules and improve the pharmacokinetics of DA. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121:1992-1998, 2011