In this work, was investigate the effect of the molecular weight of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) on the preparation of medroxyprogesterone acetate (MPA)-encapsulated polymeric nanoparticles (PNPs) using the supercritical fluid extraction of emulsions (SFEE) technique. Particles with diameters between 850 nm-183 nm were obtained using PHBV of molar mass reduced and variable between 210 kDa to 14 kDa, thus establishing a direct relation between the size of the PNPs prepared with SFEE and the molar mass of the polymer. These results were contrasted with those obtained with the conventional emulsion solvent evaporation (ESE) technique. PNPs prepared by SFEE were observed to be smaller than those produced by ESE, for all polymer molecular weights (MW) studied. The encapsulation efficiency (EE%) of MPA in the PNPs prepared with the SFEE technique, and with the lowest MW PHBV was determined to be 70%. The in vitro release kinetics for this system indicated that the mean time for 35% release of MPA was 18 h. Both a first and a second-order kinetics models provide a good fit to the release profile of MPA from the PHBV PNPs. Cellular viability results indicate low toxicity profiles of the PHBV PNPs prepared with the SFEE technique, even at high PNP concentrations. (C) 2016 Elsevier B.V. All rights reserved.