Linamarin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles were prepared by using a double emulsion solvent evaporation method using polyvinyl alcohol as a surfactant. A two-factor full factorial design, Box-Behnken design and surface response methodology, were employed to improve the nanoparticle yield, particle size, and drug encapsulation efficiency OPTIMIZING ENCAPSULATION OF LINAMARIN PLGA NANOPARTICLESby determining the optimum levels of the process parameters, namely the polymer concentration, surfactant concentration, and homogenization speed. Both linear and quadratic empirical models were developed to express each response parameter as a function of the studied factors. A total of 12 and 17 experimental runs were necessary to obtain adequate empirical models ( p < 0.05) for both factorial and Box-Behnken designs, respectively. The final optimum values for the polymer concentration, surfactant concentration, and homogenization speed were determined at 9.8 mg/mL, 50 mg/mL, and 23,000 rpm, respectively. Formulations obtained at this optimum preparing condition resulted on average 96% yield, 61.2% drug encapsulation efficiency, and 144.6 nm particle size. However, all prepared nanoparticles showed some kind of controlled drug release; most likely the final optimized nanoparticles exhibited the most biphasic controlled drug release profile with a minimal burst release and overall drug release of <30% in 120 h of incubation. C