壳聚糖／聚乙二醇琥珀酸酯丝裂霉素C释药系统的研制与体外释放实验  

DEVELOPMENT OF CHITOSAN/POLYETHYLENE GLYCOLS-SUCCINATE MITOMYCIN C FILM DRUG DELIVERY SYSTEM AND RELEASING CHARACTER IN VITRO

作　　者：张宇[1] 周初松[1] 蒋刚彪[2] 于博[1] 高飞[1] 傅栋[1] 

机构地区：[1]南方医科大学珠江医院骨科中心,广州510282 [2]华南农业大学资源环境学院制药工程系

出　　处：《中国修复重建外科杂志》2008年第5期543-547,共5页Chinese Journal of Reparative and Reconstructive Surgery

基　　金：广东省科技计划资助项目(20042070019)~~

摘　　要：目的研制壳聚糖/聚乙二醇琥珀酸酯(chitosan/polyethylene glycols-succinate,CH/PEG-SA)丝裂霉素C(mitomycinC,MMC)局部药物释放系统,观察其体外释药效果。方法将透析后的CH/PEG-SA及MMC共混后置入冻干机,冻干制得CH/PEG-SA/MMC膜片,将膜片置于10mL37℃生理盐水中浸泡,静置3个月观察其脆性。绘制100、50、25、12.5、6.25、1μg/mL MMC液与吸光度(A)值的标准曲线。将CH/PEG-SA/MMC膜片20mg浸泡于PBS液中,第1、3、5、8、12、16、18、22、26、30、32、39、60和88天取浸出液,测定药物释放浓度与时间的变化曲线,探讨膜片结构与释药的关联性。结果脆性观察:膜片浸泡3个月后不脆裂。MMC液标准曲线回归方程为:y=0.593x3-2.563x2+25.944x-0.236(R2=1.000)。药物缓释膜片中MMC均能从膜片向PBS液扩散,释放量逐渐增加,第12天释放量达最大,为14.9616μg/mL,第18、32天又出现两次释放高峰,分别为14.4824μg/mL和11.4092μg/mL,明显高于成纤维细胞50%抑制率质量浓度(ID50,10.4713μg/L);其余时间以较低浓度间断释放,且释放量逐渐减少,第60天累积释放量为0.1793μg/mL,直至药物释放完全。不同时间点浓度差异均有统计学意义(P<0.05)。结论CH-PEG-SA/MMC膜片柔韧性提高,又改善复合材料的力学性能,且成膜性更好,能更有效地避免药物突释,保持一定时间药物释放。Objective To develop the chitosan/polyethylene glycols succinate （CH/PEG-SA） mitomycin C （MMC） film drug delivery system and its release effect in vitro. Methods MMC loading in composite films was determined using a UV-visible spectrophotometer. Freeze-dried films （90 mg） were immersed in 1 mL PBS buffer （pH 7.4）. The concentrations of MMC releasing in vitro were calculated refer to the standard curve of relationshi p between the concentrations of MMC and the value of UV-visible spectrophotometer. The curve of the concentrations of MMC releasing from the films in vitro was drawn at different time. The relationship between the films, structure and the drug releasing was revealed. Results The films showed swelling without brittleness. The equation of Linear Regression was y=0.593x^3- 2.563x^2 ＋25.944x - 0.236 （R^2=1.000）. The film had a good drug delivery capability. The samples weighing 20 mg were soaked into the liquid of PBS, the releasing concentrations of MMC were 14.961 6 μg/mL at 12 days, 14.482 4 lag/mL at 18 days and 11.409 2 μg/mL at 32 days, which was higher than ID50 of MMC （10.4713 μg/L） to fibroblast. Then MMC was released at a low concentration. The releasing concentrations of MMC was 0.179 3 μg/mL at 60 days until being delivered completely. Conclusion The flexibility is enhanced, and the mechanical function is improved, so that there is better nature of membrane. The initial burst is avoided more effectively, and the drug releasing would be maintained for a certain time.

关 键 词：壳聚糖 聚乙二醇 琥珀酸酯 丝裂霉素C 药物释放系统 复合材料 

分 类 号：R94[医药卫生—药剂学]