The influence of particle size on the in vitro digestion of beta-lactoglobulin (BLG)-coated lipid nanoparticles was examined using simulated small intestine conditions. Nanoemulsions were prepared by high-pressure homogenization and organic solvent (hexane) evaporation. The effect of the initial organic phase composition on the size, microstructure, electrical properties, and digestion of the lipid nanoparticles was evaluated. The radius of the nanoparticles decreased (from 85 to 48 nm) as the solvent concentration in the initial organic phase increased (from 0% to 95%). The lipid digestion rate initially decreased with decreasing particle radius (for r = 85-59 nm), but then it increased (for r = 59-48 nm). This dependence is contrary to the usual assumption that lipid digestion increases with increasing lipid surface area. Our results suggest that the structure of the protein layer coating the lipid nanoparticles has an important effect on lipid digestion. (C) 2012 Elsevier Inc. All rights reserved.