In this work, PLGA nanoparticles were prepared by an emulsification- diffusion technique. The main objective was to optimize the preparation of formulations by evaluating the influence of the technological parameters on the physicochemical properties of PLGA nanoparticles. The effects of variations in polymer and emulsifier concentrations, and homogenization duration, rate and type on the particle size distribution, surface charge and morphology of nanoparticles were assessed. The smallest nanoparticles (177.53 ± 2.78 nm) were obtained with a 2% PLGA (w/v) concentration in the organic phase and 3% PVA (w/v) in the aqueous phase and were prepared by an emulsification-diffusion method via ultrasonic homogenization at a power of 80 W applied for 30 s. It was observed that nanoparticles prepared by Ultra Turrax® were more spherical but larger. In addition, increasing the PVA concentration in the aqueous phase, increasing the PLGA concentration in the organic phase and increasing the homogenization rate decreased the zeta potential values of PLGA nanoparticles.