【摘要】 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。更多还原

【Abstract】 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(P<0.01).The 5-Fu concentration of Group PEG-5-Fu-MAMS in liver was lowerthan that ofGroup 5-Fu-MAMS(P<0.05).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.更多还原