中文摘要：

第4代聚酰胺-胺（polyamidoamine．PAMAM）树枝状聚合物与平均分子质量5 000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（meanretention 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。

英文摘要：

Generation 4 polyamidoamine （PAMAM） dendrimer was PEGylated with polyethylene glycol （PEG） at an average molecular weight 5 000 via amide bond. PAMAM and PEGylated PAMAM （PAMAM-PEG） dendrimer were used as drug nanocarriers. Methotrexate （MTX）, an antineoplastic agent, was selected as a model drug. PAMAM/MTX and PAMAM-PEG/MTX complexes were prepared. The pharmacokinetic characters and anti-tumor activity of the PAMAM-PEG/MTX complex were studied as compared with MTX injection and PAMAM/MTX complex by intravenous injection in rats and S180 tumor bearing mice, separately. The plasma samples from normal rats were analyzed by HPLC method, and concentration-time data were analyzed using a non-compartmental analysis. Their anti-tumor effects in vivo were evaluated against S180 solid tumors in mice by measuring average tumor weight and calculating the inhibitory rate of tumor on day. 17 after successive injections. The results showed that both plasma half-life and＇mean retention time （MRT） of the complexes were longer than that of MTX injection （P〈0.01）, while the area under the plasma concentration vs time curve （AUC） of PAMAM-PEG/MTX was the largest as compared with that of free drug and PAMAM/MTX complex （P〈0.01）. The inhibitory rate of tumor of PAMAM-PEG/MTX complex enhanced 2.1 and 1.8 times over that of free drug and PAMAM/MTX complex, respectively, indicating that PAMAM-PEG/MTX exhibited thehighest antitumor activity. In summary, PEGylated PAMAM could be useful as a potential drug delivery carrier.