Poly(lactic acid-4-hydroxyproline-polyethylene glycol) (PLA-Hpr-PEG) was synthesized via melt copoly-merization with stannous chloride as a catalyst activated by a proton acid. Copolymers with different poly(ethylene glycol) (PEG) concentrations (0.1, 0.5, 1, and 5 wt %) were synthesized and exhibited moderate molecular weights (weight-average molecular weight = 9705-13,600 g/mol) and reasonable molecular weight distributions (weight-average molecular weight/number-average molecular weight = 1.35-1.66). The structure of the polymers was verified with infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. The nanoparticles were made by the nanoprecipitation method with PLA-Hpr-PEG. The size and size distribution of the nanoparticles were investigated with laser light scattering, and the surface morphology of the nanoparticles was investigated with transmission electron microscopy. The drug encapsulation efficiency and drug loading content were measured with ultraviolet absorption spectroscopy. The effects of various formulation parameters were evaluated. The prepared nanoparticles were spherical and greater than 100 nm in size. The drug loading content and encapsulation efficiency were greatly influenced by the amount of the copolymer and the volume of the solvent. The PEG content in the polymer could affect the release of drugs from the PLA-Hpr-PEG nanoparticles. (c) 2006 Wiley Periodicals, Sci.