两种5-氟尿嘧啶磁性白蛋白微球对肝脏靶向性的研究

目的：研究聚乙二醇（PEG）修饰的5-氟尿嘧啶磁性白蛋白微球（PEG-5-Fu-MAMS）和5-氟尿嘧啶磁性白蛋白微球（5-Fu-MAMS）对肝脏的被动靶向性,为实现肿瘤的主动靶向治疗,减少化疗药物对肝脏的毒副作用寻找新的途径。方法：取Wistar大鼠18只,每组6只,分为游离5-Fu组、5-Fu-MAMS组和PEG-5-Fu-MAMS组;分别将3种不同的制剂（按5-Fu8mg/kg）经尾静脉给药,30min后,经眼眶采血,处死大鼠,取其肝脏。用高效液相色谱法（HPLC）法分别检测血液和肝脏中的药物浓度。结果：PEG-5-Fu-MAMS组、5-Fu-MAMS组和游离5-Fu组肝脏中的药物浓度分别为（25.21±2.98）μg/mL、（48.03±10.28）μg/mL和（15.31±2.81）μg/mL。PEG-5-Fu-MAMS组和5-Fu-MAMS组肝脏中药物浓度明显高于游离5-Fu组（P〈0.01）,而在血清中药物浓度相反,明显低于游离5-Fu组（P〈0.01）;PEG-5-Fu-MAMS组肝脏中药物浓度明显低于5-Fu-MAMS组（P〈0.05）,血清中两者的药物浓度差别无统计学意义（P〉0.05）。结论：PEG-5-Fu-MAMS对肝脏的被动靶向作用明显减弱,有效地减轻了药物对肝脏的毒副作用,为实现肿瘤的主动靶向治疗提供了一条新途径。

Comparison of Targeting Distribution of PEG-5-Fu-MAMS and 5-Fu-MAMS in liver

Objective：To investigate the targeting distribution of PEG-5-Fu-MAMS and 5-Fu-MAMS in liver in order to reduce the side effect of chemotherapeutics and explore a better initiative targeting chemotherapy for cancer.Methods：Eighteen mice were equally divided into Group 5-Fu（n=6）,Group 5-Fu-MAMS（n=6）and Group PEG-5-Fu-MAMS（n=6）.They were injected through the vena caudalis at the dose of 8 mg/kg of free drug,respectively.30 minutes later,the animals were immediately killed after getting blood from fossa orbitalis.The concentration of 5-fluorouracil in liver was determined by the high performance liquid chromatography（HPLC）.Results：The 5-Fu concentration in liver was 15.31±2.81 μg/mL,48.03±10.28 μg/mL and 25.21± 2.98 μg/mL in Group 5-Fu,5-Fu-MS and PEG-5-Fu-MS,respectively.There were significant difference among them（P0.01）.The 5-Fu concentration of Group PEG-5-Fu-MAMS in liver was lowerthan that ofGroup 5-Fu-MAMS（P0.05）.Conclusion：The passive target ofPEG-5-Fu-MAMS to liver is significantly decreased.It is efficient to reduce the toxicity of chemotherapeutics in liver and provide a new initiative targeting chemotherapy for cancer.