Biodegradable polymeric nanoparticles are considered as promising drug delivery systems due to their high potential in tuning the release and alleviate side effects. However, particle greater than 200 nm can be detected by the immune system. Thus, this paper focuses on the elaboration of size-controlled nanoparticles of poly (lactic-co-glycolic acid) smaller than 200 nm encapsulating a model drug. For this purpose, the biodegradable polymer was first solubilized in ethyl acetate and then dispersed into water by different nanoemulsification devices: shear mixer, sonicator and elongational-flow reactor and micromixer. Last two devices showed the capacity to produce monomodal nanoparticles of targeted size range at different continuous to disperse phase volume ratios. On a second part, nanoparticles produced with the micromixer were employed as nanocarriers for rifampicin, a hydrophobic antibiotic. These drug-loaded nanoparticles were produced at different drug concentrations to study the effect of drug load on the particle properties. Different techniques such as dynamic light scattering, transition electron microscopy and ultraviolet spectroscopy were employed to thoroughly characterize the nanoparticle diameter, size dispersity and morphology, drug encapsulation efficiency and in vitro drug release profile. Nanoparticles produced with the micromixer, following a new phase pre-saturation approach, had a highly monomodal diameter as low as 63 nm and an encapsulation efficiency of 40% at 5% w/v drug load was measured. Drug release tests under sink conditions showed 44% ± 2% cumulative drug release within 8 days.