5-氟尿嘧啶控释植入剂在小鼠肿瘤组织的分布

Distribution of 5-fluorouracil controlled release implant in tumor bearing mice

目的建立5-氟尿嘧啶(5-Fu)在小鼠肿瘤组织中的分析方法,并用于考察5-Fu控释植入剂在小鼠肿瘤组织的分布。方法荷瘤小鼠瘤周植入分别由PLGA 50/50和PLGA 75/25为载体制备的5-Fu控释植入剂,RP-HPLC测定小鼠肿瘤组织中的药物浓度。结果肿瘤组织中5-Fu的线性范围为0.5～15.4μg·g-1,准确度为97.5%～104.0%,提取回收率为81.9%～88.3%,日内RSD均<2.0%,日间RSD均<7.6%。以PLGA50/50、PLGA75/25为载体的5-Fu控释植入剂在荷瘤小鼠体内的药动学参数:tmax分别为9、15 d;Cmax分别为3.79、2.83μg·g-1;AUC分别为41.15、43.50(μg·g-1)×d。结论该分析方法可用于5-Fu在肿瘤组织中的分布行为研究,2种载体的5-Fu控释植入剂均能维持小鼠肿瘤组织中较长时间的药物分布,延长药效作用时间。

Objective To establish an assay of 5-fluorouracil（5-Fu） in tumor bearing mice,and to investigate the distribution of 5-Fu controlled release implant in the tumor.Methods The 5-Fu controlled release implant prepared by PLGA 50/50 and PLGA75/25 as carriers was inserted around the tumor.The concentrations of 5-Fu in the tumor were determined by RP-HPLC.Results The linearity of 5-Fu in the tumor was 0.5-15.4 μg·g-1.The accuracy and the extraction recovery were 97.5%-104.0% and 81.9%-88.3%.The intra-day and inter-day RSD were less than 2.0% and 7.6%,respectively.The tmax,Cmax and AUC for PLGA 50/50 implant were 9 d,3.79 μg·g-1and 41.15（μg·g-1）×d,respectively.The tmax,Cmax and AUC for PLGA 75/25 implant were 15 d,2.83 μg·g-1and 43.50（μg·g-1）×d,respectively.Conclusion The method is reliable in the study of distribution of 5-Fu in tumor bearing mice.The 5-Fu controlled release implant prepared with 2 kinds of polymers could extend the duration of drugs in the tumor.