论文部分内容阅读
目的考察小鼠静脉注射重组人干扰素α2b纳米粒后的体内药动学及组织分布。方法小鼠尾静脉注射给药后,采集不同时间血液、肝、肺和肾样品,经处理后,应用双抗体夹心酶联免疫吸附法(ELISA)测定重组人干扰素α2b的血浆及组织中浓度。结果重组人干扰素α2b纳米粒及溶液注射给药,血浆药时数据经3p97药动学程序拟合,均符合一级消除动力学双隔室模型。给予重组人干扰素α2b纳米粒小鼠体内消除半衰期(t1/2β=2.786 h)是溶液剂消除半衰期的(t1/2β=0.599 h)的4.7倍;血药浓度时间曲线下面积纳米粒组是溶液剂组的3.95倍,肝组织中药时曲线下面积纳米粒制剂是溶液剂组的3.8倍。与溶液剂组相比,纳米粒组在肺、肾中的药物分布也显著增加(P<0.001)。结论纳米粒作为重组人干扰素α2b的载体,能够显著延长重组人干扰素α2b小鼠体内消除半衰期,增加其在肝、肺、肾组织中的分布。
Objective To investigate the in vivo pharmacokinetics and tissue distribution of recombinant human interferon α2b nanoparticles in mice. Methods After tail vein injection, samples of blood, liver, lung and kidney were collected at different times. After treatment, the concentrations of recombinant human interferon α2b in plasma and tissue were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA) . Results Recombinant human interferon α2b nanoparticles and solution injection administration, plasma drug data by 3p97 pharmacokinetic program fitting, are in line with the first-order elimination kinetic double compartment model. The half-life (t1 / 2β = 2.786 h) of the recombinant human interferon α2b nanoparticles was 4.7 times of that of the solution (t1 / 2β = 0.599 h); the area under the plasma concentration time curve was 3.95 times that of the solution group, and the area under the curve of the liver tissue medicine was 3.8 times that of the solution group. Compared with the solution group, the drug distribution in the lung and kidney of the nanoparticle group also increased significantly (P <0.001). Conclusion Nanoparticles as a carrier of recombinant human interferon α2b can significantly prolong the elimination half-life and increase its distribution in liver, lung and kidney of recombinant human interferon α2b mice.