中文摘要：

考察本实验室合成的N-（2-羟丙基）甲基丙烯酰胺[N-（2-hydroxypropyl）methacrylamide,HPMA]聚合物-5-氟尿嘧啶（5-flurouracil,5-FU）接合物（P-FU）的体外释药、体内分布及抗肿瘤活性。以小鼠血浆为介质,考察P-FU中5-FU的释放规律;以小鼠H22肝癌实体瘤模型（皮下型）为肿瘤模型,考察接合物在荷瘤小鼠体内的分布情况、药代动力学规律及抑瘤活性。结果表明,37℃时P-FU在小鼠血浆中具有一定的稳定性,半衰期（t1/2）为32.4 h。与5-FU相比,P-FU在荷瘤小鼠体内的循环时间明显延长（血浆中t1/2为原药的166倍）,在肿瘤中的沉积量（AUC为5-FU的3.3倍）及滞留时间（t1/2为5-FU的2.3倍）均有明显增加。体内药效学研究表明,P-FU组对荷瘤小鼠的肿瘤生长抑制率（69.09%）显著高于5-FU组（56.49%,P〈0.05）,瘤块组织病理学观察结果也显示P-FU组小鼠肿瘤组织中细胞凋亡程度大于5-FU组。HPMA聚合物可被用于为5-FU构建一种新型实体瘤高分子给药系统。

英文摘要：

The in vitro release behavior, in vivo biodistfibution and antitumor activity of N-（ 2- hydroxypropyl） methacrylamide （I-IPMA） copolymer-5-fluorouracil conjugates （P-FU） were studied. The in vitro release behavior was evaluated by determining the amount of 5-fluorouracil （5-FU） released from P-FU in mice plasma at 37 ℃. The in vivo biodistribution and therapeutic evaluation were investigated with Kunming mice bearing hepatoma 22 （ H22 ）. The in vitro half-life （ t1/2 ） of P-FU in mice plasma was 32.4 h. It appeared that the circulation life time of the conjugates were 166 times longer than that of 5-FU. The AUC and t1/2 of P-FU in tumor were 3.3 times and 2. 3 times more than those of 5-FU, respectively. Therapeutic evaluation also demonstrated that the treatment with P-FU displayed stronger inhibition of the tumor growth when compared with that of 5-FU （ P 〈 0. 05 ）. HPMA copolymer is a potential carrier for 5-FU for effective treatment of cancer.