【摘要】 【目的】探讨丝裂霉素纤维蛋白胶凝胶(MMC/FG)化疗的缓释特性。【方法】体外释放实验中,将8mg丝裂霉素(MMC)与5mL纤维蛋白胶(FG)混合成凝胶MMC/FG,将凝胶置于50mL含纤溶酶原及尿激酶的磷酸盐缓冲液(PBS)中,在37℃恒温摇床中培养。分别于开始培养15min,2、8、24、48、72、96、120h后取0.1mLPBS作样本,测试其中的MMC质量浓度,观察MMC的释放过程。体内实验中,将MMC/FG(实验组)或单纯MMC溶液(对照组)在开腹直视下注入小鼠肝脏,定时取小鼠肝脏及少量外周血作样本,测试样本中的MMC质量浓度,计算肝脏及外周血中MMC的动力学参数。【结果】体外释放实验显示,2h后MMC的累计释放率为(33.91±2.29)%,24h后为(64.46±3.18)%,96h后释放趋于平衡。动物实验显示,肝组织MMC峰质量浓度(ρmax)两组差别无统计学意义(P>0.05),外周血ρmax实验组显著低于对照组(P<0.01);肝组织及外周血MMC的消除半衰期(t1/2)及曲线下面积(AUC)实验组均明显长于或大于对照组(P<0.01)。【结论】在体内外条件下MMC/FG均有良好的缓释性,在小鼠肝脏局部使用MMC/FG,可延长MMC在肝脏的滞留时间,降低其在外周血的质量浓度。更多还原

【Abstract】 ObjectiveTo investigate the sustained release property of chemotherapy by fibrin glue enwrapping mitomycin (MMC/FG). MethodsIn vitro release study, MMC/FG was obtained by mixing 8 mg of mitomycin(MMC) with 5 mL of fibrin glue(FG). Then the glue was put into 50 mL of phosphate buffered saline (PBS) containing plasminogen and urokinase, which was incubated in a cradle at 37 ℃. Respectively, 0.1 mL of PBS was taken as sample 15 min, 2, 8, 24, 48, 72, 96, and 120 h after incubation. Concentration of MMC of each sample was determined to show the release process of MMC. In vivo study, MMC/FG (study group) or solution of simple MMC (control group) was injected into the livers of mice by celiotomy. At fixed times the livers and some peripheral blood of the mice were collected respectively as samples whose concentrations of MMC were determined. Then the pharmacokinetic parameters of MMC in livers and peripheral blood were calculated. ResultsIn vitro release study revealed that the accumulative release rate of MMC was (33.91±2.29)%2 h after incubation and it rose to (64.46±3.18)%24 h later. The release process went to a balance condition 96 h later. In vivo study indicated that there was no significant difference in the peak concentration (ρmax) of MMC in livers between groups (P >0.05) while ρmax in peripheral blood of study group was significantly lower than that of control group (P< 0.01). The elimination half-life (t1/2) and the area under curve (AUC) in both livers and peripheral blood of study group were significantly longer or larger than those of control group (P< 0.01). ConclusionsMMC/FG takes on a perfect sustained release property both in vitro and in vivo. Using MMC/FG in livers of mice locally can prolong the staying period of MMC in livers and reduce its concentration in peripheral blood.更多还原