摘要
以聚乙二醇、六亚甲基二异氰酸酯、2,2-二羟甲基丙酸为原料,采用预聚法合成了含羧基的聚氨酯(PU-COOH);PU-COOH经水合肼改性后,再与阿霉素(DOX)反应,制备了侧链键合药物的pH敏感释药型聚氨酯前药(PU-hyd-DOX)。采用核磁共振氢谱(1H-NMR)、凝胶渗透色谱(GPC)和紫外可见分光光谱(UV-vis)等手段对产物的结构进行了表征,前药中DOX的键合质量分数可达17.6%。在37℃不同pH缓冲溶液中的体外释药实验结果表明,PU-hyd-DOX具有良好的pH敏感释药性能,且在pH=7.4的缓冲溶液中对DOX无暴释。CCK-8细胞实验测试结果表明,PU-COOH对人乳腺癌细胞(MCF-7)基本无毒性,但PU-hyd-DOX对MCF-7细胞表现出良好的生长抑制作用。
Polyurethane with carboxyl side groups(PU-COOH)was synthesized by prepolymerization method,using polyethylene glycol,hexamethylene diisocyanate and 2,2-bis(hydroxymethyl)propionic acid as raw materials.Carboxyl goups in PU-COOH were modified by hydrazine,and then reacted with doxorubin.Finally,polyurethane-doxorubin prodrug with acid-sensitive drug release(PU-hyd-DOX)was obtained.The structures of the obtained products were characterized by 1H-NM R,GPC and UY-vis.The results indicated that the drug loading mass fraction of PU-hyd-DOX reached 17.6%.The in vitxo drug release experiments in different pH buffer solutions at 37°C showed that PU-hyd-DOX had hardly burst release for DOX in pH=7.4 and had good pH-sensitive drug release property.GCK-8 assay demonstrated that PU-COOH had no toxicity to MCF-7 cells and PU-hyd-DOX had excellent effects on the inhibition proliferation of MCF-7 cells.
作者
黄登程
周瑜
杨冰
陈红祥
廖兴华
王士海
HUANG Dengcheng;ZHOU Yu;YANG Bing;CHEN Hongxiang;LIAO Xinghua;WANG Shihai(Key Laboratory of Coal Conversion and New Carbon Material of Hubei Province,Wuhan University of Science and Technology,Wuhan 430081,China;Institute of Biology and Medicine,Wuhan University of Science and Technology,Wuhan 430081,China)
出处
《聚氨酯工业》
北大核心
2018年第2期12-15,共4页
Polyurethane Industry
基金
省部共建耐火材料与冶金国家重点实验室项目(2018QN13),煤转化与新型炭材料湖北省重点实验室基金项目(WKDM201105)。
关键词
聚氨酯
阿霉素
药物传递系统
酸敏感性
polyurethane
doxorubicin
drug delivery system
acid sensitivity
