ABSTRACT Mixed nanoparticles of PLA and Pluronic ® were developed to overcome the low chemical and colloidal stability in the gastrointestinal track for PLA nanoparticles. The aim of present study was to improve the stability of coating the PLA nanoparticle surface with hydrophilic polymers, such as poly(ethylene oxide). The Pluronic ® covered PLA nanoparticles were prepared through nanoprecipitation method. The method was optimized in terms of addition order, type, and concentration of Pluronic ® and stirring velocity to obtain particles with sizes around 100 nm. The ζ potential measurements and thermal analysis confirmed the formation of PEO layers around the nanoparticles. Dynamic Light Scattering studies of mixed PLA/Pluronic ® nanoparticles showed colloidal and chemical stability during storage and in simulated gastrointestinal fluids, suggesting this system as an alternative for the delivery of therapeutics via oral administration. The nanoparticles ability of encapsulating hydrophobic drugs was evaluated using Nile Red as a probe molecule. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133 , 43828.