卓仁禧院士_用于基因和抗癌药物控制释放高分子材料研究.ppt

1、用于基因和抗癌药物控制释放高分子材料研究 卓仁禧 院士 生物医用高分子材料教育部重点实验室 武汉大学化学与分子科学学院,一. 高分子基因治疗载体研究 病毒载体和非病毒载体的比较,非病毒载体 阳离子脂质体 高分子: 阳离子高分子 水溶性非离子高分子 高分子基质,常用的聚阳离子基因载体,Poly-(4-amino-butyl)-L-glycolic acid S W Kim, Utah Univ,Poly-L-lysine,Polyethylenimines (PEI) Behr J P, France,Dendrimer Szoka UCSF 聚己内酯,聚羟基丁酸及其共聚物) 聚酸酐 聚碳酸酯及

2、其共聚物 聚磷酸酯及其共聚物 纳米药物控制释放 温度敏感快速响应PNIPA水凝胶,Poly(lactide-co-glycolide) PLGA,Polylactide PLA,Polyglycolide PGA,聚碳酸酯及其共聚物,BTMC,PTMC,卓仁禧,王旭立,刘立建. 苄氧基三亚甲基碳酸酯及其制备方法。中国专利 ZL 01 1 14284.7 C07D319 /04,卓仁禧，王旭立，刘立建。聚（取代基三亚甲基碳酸酯）及其制备方法和用途。ZL01114285.5,In vitro cytotoxicity of PBTMC and PHTMC COS7 cells. Incubatio

3、n time: 24 h. Temp.: 37oC,Dependence of hydrophilicity on copolymer content,In vitro degradability of copolymers, PBS pH7.4，37oC,5-Fu release profiles of copolymers, PBS pH7.4，37oC,Zhang Y, Zhuo R X, Synthesis and drug release behavior of poly (trimethylene carbonate)poly (ethylene glycol)poly (trim

4、ethylene carbonate) nanoparticles, Biomaterials (In press),PTET triblock copolymer,纳米药物控制释放,Synthesis and properties of PTET triblock copolymers,Particle sizes, drug loading content, loading efficiency, and yield of the PTET polymeric nanoparticles,Polymeric nanoparticles were prepared by the dialys

5、is technique. Drug: methotrexate (MTX),TEM image of PTET-7 nanoparticles loaded methotrexate (MTX),Effect of molecular weight of PEG in the copolymers on the MTX release rate PBS, pH =7.4, 37 C.,Effect of content of PEG block in the copolymers on the MTX release rate PBS, pH =7.4, 37 C.,温度敏感快速响应PNIP

6、A水凝胶,A 混合溶剂法 B 相分离法 C 使用成孔剂:如PEG D 形成互穿网络 在温度敏感水凝胶领域发表SCI论文30多篇。,靶向性抗癌药物,5-Fu抗癌药物,PM liver-targeting group,肝靶向高分子抗癌药物,肝靶向高分子抗癌药物5-Fu- (99mTc DTPA)-PAEA-PM注射后不同时间在大鼠体内各器官的分布,62.5g/mL Bel-7204体外凋亡率:51%,135g/mL Bel-7204体外凋亡率:62%,Control,肝靶向高分子抗癌药物5-Fu-PAEA-PM对人体肝癌细胞(Bel-7204 )的体外凋亡实验的荧光照片,P(TMC-co-EEP)

7、,Porcine Pancreas Lipase (PPL) Candida Rugosa Lipase (CL) Al(OiPr)3,酶催化开环聚合反应,Ring-opening copolymerization of TMC and EEP catalyzed by enzymes,Polymerization catalyzed by PPL immobilized on silica microparticles (PISM),Effect of lipase concentration on Mn and yield,Time dependence of Mn and yield d

8、uring polymerization,Dependence of Mn and yield on the immobilized lipase PPL recycling time,Reaction temperature: 100. Reaction time: 24h,Polymerization of DTC catalyzed by PPL A immobilized on silica microparticles B immobilized on silica nanoparticles,Recycling time of IMPPL vs Mn of Poly(DTC) obtained at 130C for 4 day-polymerization,Poly (DTC) The original IMPPL The first recycling IMPPL The