AIM To improve the treatment efficacy and reduce the side effect of
5 fluorouracil (5 Fu), liver targeted 5 Fu solid
lipid nanoparticles (5 FuE SLN) were prepared. METHODS 5 Fu as model drug, was esterified with stearyl chloride. The resulted compound N 1 stearyl 5 Fu (prodrug) was determined by nuclear magnetic resonance and infrared spectrometry. The prodrug was used to prepare 5 Fu solid lipid nanoparticles (5 FuE SLN) by the method of physical agglomeration. Transmission electron microscopy was employed to study the shape, mean size and particle distribution of 5 FuE SLN. The drug loading, the in vitro drug release characteristics, the in vivo drug distribution and
pharmacokinetics in animal were also investigated. RESULTS The finding showed that the average diameter was 240 19 nm, drug loading was 20 53%. The in vitro release characteristics investigated fitted to first order pharmacokinetic model. In order to investigate the targeting effect of 5 FuE SLN, the concentrations of
5 fluorouracil in plasma, liver, lung, heart, spleen and kidney of mice were determined by high performance liquid chromatography (HPLC) after intravenous administration. The study on in vivo distribution indicated that the fate of 5 FuE SLN was different from that of free 5 Fu. The mean content of 5 Fu in liver was 67 3% for 5 FuE SLN group, 37 52% greater than the control group. It was demonstrated that 5 FuE SLN has selective targeting to liver tissue. The pharmacokinetics of 5 FuE SLN lyophilized powders in rabbits after intravenous administration was studied by HPLC. The plasma concentration time curve of 5 FuE SLN obeyed two compartment model. The pharmacokinetic parameters of 5 FuE SLN were as follows: V c=0 043361 L·kg -1 , T 1/2 α= 0 080714 h, T 1/2 β=1 283457 h, CL s=0 163265 L·h -1 . CONCLUSION Using prodrug to enhance drug liposoluble properties and the method of preparation of the liver targeted 5 FuE SLN lyophilized powders by physical agglomeration presented in this paper seem to have significant advantages and important reference value.