Targeting, internalization, and intracellular trafficking of carriers are key processes in drug delivery to endothelial cells. We synthesized PLGA particles with spherical and elliptical disk geometries and investigated the effect of particle shape on rate of particle endocytosis and their intracellular distribution in endothelial cells. Elliptical disks (aspect ratio of 5) were endocytosed at a slower rate compared to spheres (1.8 mu m diameter) of the same volume. However, both particles were eventually internalized and accumulated around the nucleus. We quantified the orientation of elliptical disks and found that disks, on average, oriented tangentially with the nuclear membrane. The non-spherical geometry of elliptical disks brings unique aspects to the kinetics and equilibrium distribution of these particles in cells.