Propranolol-HCI incorporated nanoparticles prepared with a blend of a polyester and a polycationic polymer and coated or not with a low molecular weight heparin by electrostatic interactions were prepared by emulsification followed by solvent evaporation. The mean diameter was 388 and 357 nm for coated and uncoated nanoparticles, respectively, and the entrapment efficiency ranged from 20 to 32%. Coated nanoparticles were negatively-charged, whereas uncoated nanoparticles displayed a positive zeta potential (+30 mV). After intravenous administration to rabbits of propranolol-HCI solution and propranolol-loaded nanoparticles coated or not with heparin, pharmacokinetic data revealed that coated nanoparticles exhibited a prolonged blood residence time. It can be concluded that the hydrophilic layer of heparin at the surface of nanoparticles conferred stealth properties which probably reduce the phagocytosis process and avoid immediate uptake by the mononuclear phagocytic system.