Novel biodegradable amphiphilic ABA triblock copolymers, i.e. poly(3(S)-methyl-morpholine-2,5-dione-co-p-dioxanone)-block-poly(ethylene glycol)-block-poly(3(5)-methyl-morpholine-2,5-dione-co-p-dioxanone) [P(MMD-co-PDO)-b-PEG-b-P(MMD-co-PDO)1, were successfully prepared by ring-opening polymerization of 3(5)-methyl-morpholine-2,5-dione (MMD) and p-dioxanone (PDO) in the presence of poly(ethylene glycol) 6000 as an initiator. These triblock copolymers were characterized by H-1 NMR, C-13 NMR, Fourier transform infrared, gel permeation chromatography and differential scanning calorimetry measurements. P(MMD-co-PDO)-b-PEG-b-P(MMD-co-PDO) could self-assemble into stable nanosized microspheres with critical micellar concentrations of 0.41-0.66 mu g/mL. The microspheres showed high hydrolytic degradation. In addition, doxorubicin (DOX) was chosen as a model drug and successfully encapsulated into the microspheres by hydrogen-bond interaction and hydrophobic effect. The transmission electron microscopy and dynamic light scattering measurements revealed that these microspheres were ellipsoidal nanoparticles with diameters ranged from 50 to 100 nm. These copolymer microspheres exhibited high loading capacity (LC), encapsulation efficiency (EE) of DOX and sustained drug release behavior in phosphate buffered solution (PBS). Moreover, the release rate of DOX from those microspheres in pH 4.0 PBS was faster than that in pH 7.4 due to pH sensitivity of the polymer-drug systems and the degradation of the matrix polymers. These amphiphilic depsipeptide multiblock copolymers would be potential promising carriers for anti-tumour drug delivery. (C) 2013 Elsevier Ltd. All rights reserved.