A series of amphiphilic triblock copolymers, methoxy poly(ethylene glycol)-b-poly(octadecanoic anhydride)-b-methoxy poly(ethylene glycol) (mPEG-b-POA-b-mPEG), were prepared via melt polycondensation of methoxy poly(ethylene glycol) (mPEG) and poly(octadecanoic anhydride) (POA). mPEG-b-POA-b-mPEG were characterized by FTIR, ¹H-NMR, GPC, DSC and XRD. Stable drug-loaded mPEG-b-POA-b-mPEG nanoparticles (NPs) with sphere morphology and narrow size polydispersity index were prepared by nanoprecipitation technique with paclitaxel as the model drug. In vitro release behaviors of drug-loaded NPs present biphasic process and the release mechanism of each phase is zero order drug release. In vitro cytotoxicity tests investigated by MTT assay indicate that mPEG-b-POA-b-mPEG are non-toxic to normal mouse lung fibroblast cells (L929). According to this study, mPEG-b-POA-b-mPEG NPs could serve as suitable delivery vehicles for paclitaxel and other hydrophobic drugs.