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第4代聚酰胺-胺(polyamidoamine,PAMAM)树枝状聚合物与平均分子质量5000的聚乙二醇(polyethylene glycol,PEG)通过酰胺键共价结合得PAMAM-PEG。分别以PAMAM和PAMAM-PEG为抗肿瘤药物甲氨喋呤(methotrexate,MTX)的纳米载体,制备了PAMAM/MTX和PAMAM-PEG/MTX复合物,考察复合物在大鼠体内药动学行为及对S180荷瘤小鼠的抗肿瘤作用。采用高效液相色谱法测定大鼠血浆样品中MTX浓度并计算药动学参数;S180荷瘤小鼠连续给药后第17天测定瘤重并计算肿瘤抑制率。结果显示,两种复合物的大鼠血浆半衰期(plasma half-life,t1/2)和平均滞留时间(mean retention time,MRT)均较原药组显著延长(P<0.01);PAMAM-PEG/MTX复合物的血药浓度-时间曲线下面积(area under the plasma concentration vs.time curve,AUC)比原药组和PAMAM/MTX组显著增大(P<0.01)。PAMAM-PEG/MTX复合物的肿瘤抑制率分别是原药组和PAMAM/MTX的2.1和1.8倍。可见,以PEG化PAMAM为载体制备的MTX复合物在体内滞留时间延长,抗肿瘤活性提高,有望成为一种新型抗肿瘤药物载体材料。
The fourth generation polyamidoamine (PAMAM) dendrimer was covalently bound to polyethylene glycol (PEG) with an average molecular mass of 5000 by PAMAM-PEG. PAMAM and PAMAM-PEG were respectively used as nanocarriers of methotrexate (MTX) to prepare PAMAM / MTX and PAMAM-PEG / MTX complex. The pharmacokinetics of PAMAM and PAMAM-PEG / Antitumor effect on S180 tumor-bearing mice. The concentration of MTX in rat plasma samples was determined by HPLC and the pharmacokinetic parameters were calculated. On the 17th day after administration of S180 tumor-bearing mice, the tumor weight was measured and the tumor inhibition rate was calculated. The results showed that the plasma half-life (t1 / 2) and mean retention time (MRT) of the two complexes were significantly longer than those of the original drug group (P <0.01) The area under the plasma concentration vs. time curve (AUC) of MTX complex was significantly higher than that of the original drug group and the PAMAM / MTX group (P <0.01). The tumor inhibition rate of PAMAM-PEG / MTX complex was 2.1 and 1.8 times that of PAMAM / MTX respectively. It can be seen that the MTX complex prepared by using PEG PAMAM as a carrier has the advantages of prolonging residence time in vivo and increasing antitumor activity, and is expected to be a new type of antitumor drug carrier material.