可注射乙酰化乙二醇壳聚糖/泊洛沙姆复合水凝胶的制备及药物缓释研究  

Preparation of injectable N-acetyl glycolchitosan/poloxamer composite hydrogelfor drug release

作　　者：李进 候冰娜 韩超越 倪凯 赵梓年 李征征 LI Jin;HOU Bing-na;HAN Chao-yue;NI Kai;ZHAO Zi-nian;LI Zheng-zheng(College of Chemical Engineering and Materials,Tianjin University of Science&Technology,Tianjin 300457,China;Tianjin Key Laboratory of Pulp and Paper,Tianjin University of Science&Technology,Tianjin 300457,China;State Key Laboratory of Molecular Engineering of Polymers,Fudan University,Shanghai 200433,China;Tianjin Key Laboratory of Marine Resources and Chemistry,Tianjin University of Science&Technology,Tianjin 300457,China)

机构地区：[1]天津科技大学化工与材料学院,天津300457 [2]天津科技大学天津市制浆造纸重点实验室,天津300457 [3]复旦大学聚合物分子工程国家重点实验室,上海200433 [4]天津科技大学天津市海洋资源与化学重点实验室,天津300457

出　　处：《材料工程》2020年第5期83-90,共8页Journal of Materials Engineering

基　　金：2018年度天津市教委科研计划项目(2018KJ110);天津市海洋资源与化学重点实验室(201706);天津市制浆造纸重点实验室开放基金资助项目(201809)。

摘　　要：泊洛沙姆(poloxamer)是一种温敏性聚合物,在浓度为15.0%(质量分数,下同)~30.0%时可形成凝胶。为改善泊洛沙姆在体温下的成胶浓度和药物缓释性能,以泊洛沙姆407为基底,与新型温敏性乙酰化乙二醇壳聚糖复合,制得了温敏性乙酰化乙二醇壳聚糖/泊洛沙姆复合水凝胶。通过傅里叶变换红外光谱(FT-IR)、试管倒置法、旋转流变仪、扫描电子显微镜(SEM)和紫外-可见分光光度计(UV-vis)对乙酰化乙二醇壳聚糖/泊洛沙姆的结构、温敏性、力学性能、微观形貌和体外药物释放性能进行表征。结果表明,乙酰化乙二醇壳聚糖/泊洛沙姆溶液具有热可逆温敏性溶胶-凝胶转变行为。通过控制乙酰化乙二醇壳聚糖/泊洛沙姆的质量比,能够使溶胶-凝胶转变温度处于室温与体温(25~37℃)之间,缩短凝胶化时间(382s),降低泊洛沙姆407在体温下的成胶浓度(6%)。乙酰化乙二醇壳聚糖/泊洛沙姆复合水凝胶具有高度孔隙化的三维结构,其孔径大小处于10~60μm范围内,且表现出较高的力学性能。乙酰化乙二醇壳聚糖/泊洛沙姆复合水凝胶对抗癌药物吉西他滨具有缓释作用,载药凝胶的释药时间可达72 h。乙酰化乙二醇壳聚糖/泊洛沙姆复合水凝胶在可注射药物缓释载体方面具有重要的应用前景。Poloxamer is a thermo-sensitive polymer that can form gel at a concentration of 15.0%(mass fraction,the same as below)-30.0%.In order to decrease the gelatinization concentration and improve drug release properties of poloxamer at body temperature,thermo-sensitive N-acetyl glycol chitosan/poloxamer composite hydrogel was prepared by complexing N-acetyl glycol chitosan with poloxamer 407(GC/P 407).The structure,thermo-sensitivity,mechanical properties,morphology and in vitro drug release properties of GC/P 407 were characterized by FT-IR,tube inverting method,rheometer,SEM and UV-vis spectroscopy.The GC/P 407 solution shows reversible thermo-sensitive sol-gel transition behavior,and the sol-gel transition temperature is well controlled in the range of 25-37℃ by regulating the ratio of GC/P 407,which shortens the gelation time and the gelatinization concentration(6%)of poloxamer 407 at body temperature.GC/P 407 composite hydrogel,which has a highly porous three-dimensional structure with pore size of 10-60μm as demonstrated by SEM,exhibits high mechanical properties.In addition,the GC/P 407 composite hydrogel shows sustained release behavior of the anticancer drug gemcitabine,and the release time of the drug-loaded gel can reach 72h.GC/P407 composite hydrogel shows the potential for biomedical application as injectable drug delivery carrier.

关 键 词：泊洛沙姆 乙酰化乙二醇壳聚糖 溶胶-凝胶转变 药物缓释载体 

分 类 号：O648.17[理学—物理化学]