Metaxalone (Met), a drug for treatment of pain and stiffness due to muscle injuries, was covalently linked to dextran via a chloroacetyl chloride spacer. The average molecular weights of dextran are 20,000 (D-20000) and 40,000 (D-40000), respectively, and the procedure of chemical modification for dextrans was conducted by a two-step protocol: (1) synthesis of N-chloroacetyl-metaxalone; (2) synthesis of D-20000-Met and D-40000-Met. The controlled drug release studies were performed in buffer solutions with pH values of 1.1, 7.4, and 10.0. The results demonstrate that, under the same condition, the rate of release for D-20000-Met is slower than that of D-40000-Met, and more amount of Met can be detected releasing from polymer-drug conjugate at the presence of alpha-chymotrypsin in a buffer solution with pH = 8.0. It was also found that these novel polymer-drug conjugates can effectively improve the Met's pharmacokinetics, and can increase its half-life period. (c) 2007 Wiley Periodicals, Inc.