We developed a three-component, one pot biocatalytic polymerization to prepare amphiphilic diblock methoxy poly(ethylene glycol)-b-poly(profen amide -co- esters) (mPEG-PPAE) copolymers under the catalysis of Novozym-435 performed in diphenyl ether at 85 degrees C in vacuum for 48 h. Thirteen mPEG-PPAE copolymers with different profens, dicarboxylates, or PEG were designed and prepared as carriers for the sustained release of the ketoprofen, naproxen and ibuprofen amides. Their structure was characterized by FT-IR, H-1 NMR and GPC measurements. These copolymers can readily self-assemble into nanosized micelles with the well dispersed sphere in aqueous solution, which were confirmed by DLS and TEM. The size of the micelles was influenced by the copolymer concentrations, and the higher copolymer concentration lead to the smaller size. The in vitro ibuprofen amide sustained release behavior indicated that the copolymer is highly sensitive to acid environment, and the release of ibuprofen amide can be effectively controlled. (C) 2011 Elsevier Ltd. All rights reserved.