Abstract: AIM To investigate the specific brain drug targeting of 5-fluoro-2′-deoxyuridine (FUdR) by synthesis of 3′,5′-dioctanoyl-5-fluoro-2′-deoxyuridine (DO-FUdR) and incorporation into DO FUdR pharmacosomes (DO-FUdR-PS). METHODS DO-FUdR-PS was prepared by thin-layer ultrasonication technique.In vitro drug release was studied in pH 7.4 phosphate-buffered saline containing 0.3% pancreatic enzyme at 37℃ using bulk equilirium reverse dialysis bag technique. The concentration of FUdR in various organs were determined by reversed phase HPLC after iv administration of DO-FUdR-PS and FUdR. RESULTS The mean particle size of DO-FUdR-PS was 76 nm with drug loading of 29.02% and entrapment efficiency of 96.62%. The in vitro drug release kinetics could be characterized by bioexponential equation. Compared with FUdR injection, DO-FUdR-PS showed high concentration in tested organs. The brain AUC ratio of DO-FUdR-PS to FUdR was 10.97. CONCLUSION DO-FUdR-PS showed a good targeting efficiency in vivo. PS can improve the ability of drug to cross blood brain barrier and is a promising drug targeting system for the treatment of central nervous system disorders.