5-氟尿嘧啶磁性纳米脂质体在大鼠肝癌模型体内的靶向分布

目的经肝动脉给予5-氟尿嘧啶磁性纳米脂质体(MNLF),研究其在大鼠肝癌模型体内的分布。方法建立肝癌大鼠模型,随机分为3组,经肝动脉给药,A组予5-Fu溶液、B组予MNLF、C组予MNLF肿瘤区加磁场,高效液相色谱仪测量给药半小时后各组织的药物浓度,并比较不同给药方式下各组织药物浓度及肝肿瘤与各组织药物浓度比值;肝肿瘤与正常肝组织进行病理切片观察在磁场作用下,MNLF经肝动脉给药的肝肿瘤靶向性。结果经肝动脉给药30min后,C组肝肿瘤部位药物浓度较A及B组明显升高,而心、肺、肠、肾和脾等肝外组织及正常肝组织药物浓度较后2组低,肝肿瘤的药物选择指数显著升高,B组肝肿瘤的药物选择指数亦较A组升高,差异均有显著性(P<0.01)。结论MNLF经肝动脉给药并配合外加磁场治疗肝肿瘤,具有明显的肿瘤靶向性,非靶器官分布明显减少;在不加磁场情况下,MNLF对肝肿瘤仍具有一定的靶向性,但较加磁场情况下选择性降低。

Target distribution of magnetic nano-liposome loaded with 5-fluorouracil(MNLF)in rat with liver cancer

Objective] To research the targeting function of MNLF in body distribution in rat model of liver cancer. Methods] The transplanted rat liver cancer model was established and divided into three groups for A, B and C. In group A free 5-Fu was injected into hepatic artery but instead of MNLF for group B and group C. In group C the tumor field was exposed to magnetic field at the same time. The medicine concentration of each organ or tissue was measured with high performance liquid chromatogram 30 minutes after given medicine. The medicine concentration of each tissue and the concentration ratios of liver tumor to each tissue were analyzed statistically. Some of the liver tumor tissue and normal liver tissue were examined for histology and drug distribution was observed through microscope in order to investigate the targeting fuction of MNLF in the presence of magnetic field. Results] 30 minutes after the drug was injected into liver artery, the drug concentration of liver tumor of MNLF with magnetic field group (group C) was remarkable higher than those of free 5-Fu group (group A) and MNLF without magnetic field group (group B), but that of normal liver and tissues outside liver was lower. The drug selective index of liver tumor of the group C was significantly higher than those of other groups, and the drug selective index of liver tumor of MNLF without magnetic field group was also higher than that of free 5-Fu group. All of them had statistical meaning(P <0.01). Conclusions] The MNLF injected via liver artery in the presence of magnetic field magnetic field had a remarkable targeting function to liver tumor and the concentration of drug in no-targeted organ obviously decreased. In the absence of magnetic field, MNLF had yet targeting function to the liver cancer in some extent, but which was lower than that in the presence of magnetic field.