This study investigates the synthesis of diblock copolymers, the effects of preparation variables on formulation characteristics and the release rate of docetaxel loaded nanoparticles. PLGA-mPEG diblock copolymers were synthesized by ring opening polymerization reactions using stannous octoate as a catalyst and characterized by 1H NMR, FT-IR, and GPC. Docetaxel (antineoplastic) loaded nanoparticles were prepared by the emulsion solvent evaporation technique (o/w emulsification) using sodium cholate as a surfactant. To optimize the preparation conditions of the nanoparticles, the effects of preparation variables such as amount of polymer, organic to aqueous phase ratio, surfactant concentration and drug loading on the formulation characteristics were studied and evaluated in terms of particle size and drug entrapment efficiency (DEE). The nanoparticles were characterized for their size, DEE, surface charge, and surface morphology. Further, effects of the mPEG chain length (mPEG 2 and 5 KDa) in synthesis and nanoparticles formulation were examined. The results showed that the mPEG chain affected the yield and molecular weight of the copolymer substantially, whereas, least on the drug loading and nanoparticles size. The release behavior of docetaxel from the polymer matrix exhibited a biphasic pattern that is characterized by an initial burst, followed by a slower sustained release in all formulations. Copyright © 2007 American Scientific Publishers All rights reserved.