Purpose: To design, formulate and characterize sustained-release formulations of dexketoprofen trometamol (DT) nanoparticles (NPs) Methods: Dexketoprofen trometamol (DT)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs were produced by double emulsion-solvent evaporation method. The NPs were variously characterized for drug loading and release, particle profile, as well as by thermal analysis, x-ray difraction (XRD), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance analysis (H-1-NMR). Furthermore, the NPs were evaluated for cytotoxicity against NIH-3T3 cells by 3-(4, 5-dimethylthiazol-2-Yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: The DT-loaded NPs demonstrated nanostructural characteristics and extended drug release. Particle size was in the range of 243 and 295 nm which remained unchanged in drug stability testing in simulated gastrointestinal media. Encapsulation efficiency ranged from 49 - 64 % for all the formulations. Higuchi and Korsmeyer-Peppas were the best-fit release kinetic models for the NPs containing 5 and 10 % DT, respectively. The NPs with 10 % DT presented no significant cytotoxicty at the doses and periods studied. Conclusion: Stable and non-toxic DT NPs with potential for sustained and controlled release of the drug have been successfully developed.