This study aimed to explore and extend the application potential of poly(n-butylcyano-acrylate) (PBCA) nanoparticles to cross the blood-brain barrier (BBB) and to deliver their content into the central nervous system. PBCA particles were prepared by a new and efficient mini-emulsion method with excellent yield and reproducibility. These nanoparticles were loaded with 1.5% (w/v) fluorescein-isothio-cyanate-dextran (FITC-dextran), 1.5% rhodamine-123 or 7.3% doxorubicin. Particles were characterized by dynamic light scattering determining particle size, polydispersity index and zeta-potential. They were coated with 10% w/v polysorbate 80 and administered to rats. Cryosections of the brain were prepared and time-dependent distribution of fluorescence was studied. After the administration of polysorbate 80-coated particles by carotic injection, fluorescence could first be detected in capillary lumina with a progressive shift to capillary endothelial cells at 30min and a rather evenly spread distribution across the brain tissue at 60min after administration. 60min after administration into the tail vein, fluorescent particles could be assigned to endothelial cells, whereas after 2h a rather evenly spread distribution across the brain tissue was seen. These observations indicate that surface-coated PBCA nanoparticles are able to cross the blood-brain barrier and to serve as a drug-delivery system to the central nervous system.