目的　为了提高氟尿嘧啶 (5 Fu)的疗效 ,降低其毒副作用 ,制备具肝靶向的 5 Fu类脂纳米粒。方法　利用氟尿嘧啶与硬脂酰氯进行反应 ,制备了 5 Fu前体药物N1 硬脂酰 5 Fu ,通过红外光谱及核磁共振谱对合成的目标化合物进行结构确认。同时研究了前体药物的性质及稳定性。采用物理凝聚法制备类脂纳米粒 ,并研究其形态、粒径及粒径分布、载药量、体外释药特征、动物体内分布与药代动力学参数等。结果　平均粒径dav=2 40 19nm ,载药量为 2 0 5 3 %。体外释药速率符合一级动力学模型。与 5 Fu水针剂比较 ,类脂纳米粒组在肝脏中药物含量平均增加了一倍以上。家兔体内主要药动学参数为 :Vc=0 0 4336L·kg-1,T1/ 2 β =1 2 834h ,CL =0 16 32L·h-1。结论　利用前体药物可提高药物的脂溶性 ,首次以物理凝聚法制备类脂纳米粒 ,小鼠体内分布研究表明类脂纳米粒有明显的肝靶向 ,有一定的优越性和参考价值 Objective To improve the efficacy of 5-fluorouracil (5 Fu) and reduce its toxicity, a 5-Fu lipid nanoparticles with liver targeting was prepared. Methods 5-fluorouracil N-stearyl 5 Fu was prepared by the reaction of 5-fluorouracil and stearyl chloride. The structures of the target compounds were confirmed by IR and 1H-NMR. The nature and stability of the prodrugs were also studied. Lipid nanoparticles were prepared by physical coacervation, and the morphology, particle size and particle size distribution, drug loading, in vitro release characteristics, in vivo distribution and pharmacokinetic parameters were studied. Results The average particle size dav = 2 40 19nm, drug loading of 2053%. In vitro release rate in line with the first-order kinetic model. Compared with 5 Fu water injection, lipid nanoparticles in the liver increased the average drug content more than doubled. The main pharmacokinetic parameters of rabbits were: Vc = 0 4336L · kg-1, T1 / 2 β = 12 834h, CL = 0 16 32L · h-1. Conclusion The use of prodrugs can improve the liposolubility of drugs. The lipid nanoparticles were prepared by physical agglutination for the first time. The in vivo distribution of the lipid nanoparticles in the mice showed obvious liver targeting with some advantages and reference values