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。
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.
出处
《药学学报》
CAS
CSCD
北大核心
2008年第11期1152-1156,共5页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(30500636)
教育部"新世纪优秀人才支持计划"项目(NCET-06-0786)
