重组人干扰素α-2b纳米粒小鼠体内药物动力学及组织分布

Pharmacokinetics of nanoparticles containing recombinant human interferon α-2b in mice

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 study the pharmacokinetics and tissue distribution in mice after i. v. injection of recombinant human interferon α-2b（rhIFN α-2b） nanoparticles and solution. Methods The experiment was done by intravenous administration in mice and then the samples of blood, liver, lung and kidney were gathered at indicated time. The double antibody sandwich enzyme-linked immunsorbent assays method（ELISA） was used to determine the level of IFN α-2b in plasma and the tissues. Results The concentration-time curves of the nanoparticles and solution of rhIFN α-2b were fitted to double-compartment model. Half-life value of rhIFN α-2b nanoparticles（ t1/2β = 2. 786 h） was 4.65 times of that of solution（ t1/2β = 0. 599 h） ; The level of rhIFN α-2b nanoparticles in liver, lung and kidney was significantly increased and half-life was prolonged. The AUC0-∞ of rhIFN-α2b in plasma obtained from rhIFN-α2b nanoparticles -treated animals was 3.95 times greater than that obtained from solution-rhIFN-α2b -treated animals. Conclusions RhIFN α-2b nanoparticles could significantly prolong the half-life of rhIFN α-2b and increase the content of rhIFN α-2b in liver, lung and kidney.