Methoxy-poly(ethylene glycol)-block-poly(L-lactide-random-glycolide) (mPEG-PLGA) with relatively high monomer conversion, fixed LA/GA ratio, controlled molar mass, and random PLGA sequences was synthesized under microwave irradiation at 120 degrees C. The microstructure, i.e., the sequence of lactyl and glycolyl units, of the PLGA block was analyzed using proton and carbon-13 nuclear magnetic resonance spectroscopy. It was found that the second mode transesterification of glycoldyl units (-GG-) happened shortly after the reaction started and lasted during the reaction, and that of lactidyl units (-LL-) happened gradually from 1 to 30 min under microwave. Compared with traditional oil-bath heating copolymerization, microwave irradiation not only greatly increases polymerization rate but also induces rapid transesterification and achieves high randomness of the PLGA block at low reaction temperature. Nanoparticles with diameter ranging from 60 to 100 nm were also prepared from these mPEG-PLGA copolymers with varied molar mass of PEG (2k and 5k g/mol) and PLGA blocks (20k-160k g/mol), showing such block copolymer can be harnessed as drug delivery matrix in nanomedicine. (C) 2017 Elsevier Ltd. All rights reserved.