促黄体激素释放激素修饰的甲氨蝶呤体内释放研究

In vivo release study of methotrexate modified by luteinizing hormone-releasing hormone

目的研究促黄体激素释放激素修饰的甲氨蝶呤(LHRH-MTX)在模型动物体内释放MTX情况。方法建立HPLC的分析方法,经尾静脉注射给药,测定荷瘤裸鼠血液和组织中的药物浓度;与MTX制剂比较,评价LHRH-MTX在体内释放MTX情况。结果建立的HPLC分析方法回收率高于85%,日间和日内精密度(RSD)均小于10%,符合生物样品分析要求;静脉注射给药后,经统计学分析,与MTX制剂相比,LHRH-MTX释放的MTX在血浆、肝脏、肾脏的浓度有明显下降(P<0.05),而在肿瘤组织有明显提高(P<0.05)。结论所建立的HPLC用于LHRH-MTX体内释放研究结果良好,LHRH-MTX释药后MTX在体内的组织分布有明显的改变,在肿瘤部位有明显的浓集。

Objective To study the in vivo release of methotrexate（MTX） from luteinizing hormone-releasing hormone（LHRH） modified MTX in model animals.Methods A total of 60 nude BALB/c mice received a subcutaneous injection of MCF-7 cells,and 50 of them with tumor mass in size of 1.5 cm served as model animals.These mice were further divided into 2 groups,and received an injection of 10 mg/kg MTX and 28 mg/kg LHRH-MTX respectively by tail vein.Then the animals were killed at 1,2,4,12 and 24 h after injection（5 mice at each time points）,and their blood and heart,liver,spleen,kidney and tumor mass were collected.A HPLC method was established to determine the concentrations of drugs in the plasma and other tissues of the tumor-bearing nude mice.Compared with MTX injection,the capacity of the in vivo release of MTX from LHRH-MTX was evaluated.Results The recoveries of our established HPLC method were more than 85%,and the relative standard deviations of the intra-day and inter-day were lesser than 10%.After venous administration,the concentrations of MTX from LHRH-MTX group were higher in tumor tissues（P0.05）,but lower in the plasma,liver and kidney（P0.05）.Conclusion Our established HPLC method is easy to determine the in vivo release of LHRH-MTX.LHRH-MTX significantly changes the distribution of MTX in vivo and evidently increases the concentrations of MTX in the tumor tissues.