Factorial design optimization and characterization of poly-lactic acid (PLA) nanoparticle formation for the delivery of grape extracts. 
Proanthocyanidins (PAs) extracted from grapes have several bioactive properties, giving them potential medical uses.  However, PAs are unstable in the digestive tract and must be stabilized to allow oral administration, which can be accomplished by nanoencapsulation.  In this study, PAs extracted from grape seed and skin were stabilized with poly-d,l-lactide (PLA) polymer by the emulsion-evaporation method.  An experimental Box-Behnken design was implemented, evaluating the influence of three factors: sonication time (30-360s) for the emulsion formation, loading of grape extracts (5-20%) and concentration of stabilizing agent (polyvinyl alcohol, PVA: 1-3%).  The process was optimized to achieve higher encapsulation efficiency (EE=82.7%) and a smaller size (256 nm).  The nanoparticles (NPs) were physically analyzed by TEM, FT-IR, TGA and DTG to characterize the nanoencapsulation process.  In vitro release studies, through stomach and intestinal simulation, showed a sustained release of PAs from PLA-NPs.