摘要
目的:研究抗肿瘤药物载体的不同浓度纤维蛋白胶对抗肿瘤药物释放的影响。方法:(1)配制抗肿瘤药物与不同浓度纤维蛋白胶混合制剂。(2)纤维蛋白胶缓释药粒体外试验。(3)动物实验:把纤维蛋白胶甲氨蝶呤缓释药粒植入兔胫骨上端进行体内释放实验,并与静脉注射相同剂量甲氨蝶呤进行比较。结果:(1) 纤维蛋白胶MTX缓释剂的药物释放与纤维蛋白浓度有关。体内外试验表明在释放初始时低及高纤维蛋白浓度组均有较高药物释放,后期药物释放量与纤维蛋白浓度呈负相关。(2)三组低、中、高不同浓度纤维蛋白胶缓释药粒,可使MTX在局部骨组织中维持有效含量达3周,中浓度组在第4周仍有较高有效含量。且骨组织中最高含量是静脉注射相同剂量时骨含量300倍以上,但血浆峰值浓度仅为静脉组血浆峰值七分之一以下。结论:(1)纤维蛋白胶体浓度变化不仅影响胶体密度,而且影响所含药物浓度。药物释放量与两者相互作用有关。(2)三种低、中、高不同浓度纤维蛋白胶体与MTX制成的缓释药粒具有良好的缓释功能。该缓释药粒 MTX的1次局部用量可超过静脉注射1次用量的7倍以上,能较好的满足骨肿瘤局部化疗用药量大,维持时间较长,血浆药物浓度低,全身反应小的用药要求。(3)维持骨肿瘤局部较高的药物含量,及较长的时间宜选取用中等浓度的纤维蛋白胶体。
Objective：To determine the effects of different concentrations of fibrin glue as an anti-cancer drug cartier on the release of anti-cancer drugs. Methods： the slow-degrading drug delivery system （DDS） was prepared using fibrin glue mixed with methotrexate, tested for drug release in vitro, and further studied for its in-vivo performance by implanting it into the intercondylar area of tibia in rabbits, compared to controls receiving the same dose of intravenous MTX. Results： The release of MTX was related to the concentration and biodegradation of fibrin glue. Both in-vitro and in-vivo experiments demonstrated that low or high concentration groups presented with high drug release during the early stage, but the release was negatively correlated with fibrin concentration at the later time spots. Three different concentrations of fibrin glue maintained effective bone level of MTX for three weeks, and even up to four weeks in the intermediate concentration group. The maximum bone level of MTX in DDS-implanted rabbits was 300 times higher than that in rabbits treated with IV MTX, whereas the maximum plasmal level of MTX was no more than 1/7 compared with the latter. Conclusions： Fibrin concentration affects not only the fibrin glue density but also the MTX level. MTX-loaded fibrin glue drug delivery system （DDS） showed good sustained release profiles, with one single dose of local MTX-DDS providing a bone MTX level 7 times more than did a same dose of IV MTX, therefore meeting the needs （large dose, long time sustaining, low plasmal level and mild systemic reaction） of local chemotherapy for bone tumor. Intermediate concentration of fibrin glue is preferable for DDS.
出处
《广州医学院学报》
2005年第6期15-17,共3页
Academic Journal of Guangzhou Medical College
关键词
骨肉瘤
纤维蛋白胶
药物缓释系统
局部化疗
兔
fibrin glue
osteosarcoma
carrier
local chemotherapy
drug delivery system
rabbit
作者简介
白波（1960.4-）,男,教授,博士.研究方向：骨科和材料研究.
