紫杉醇PCL—PEG—PCL温敏性缓释凝胶的制备及性能研究  

Study on injectable paclitaxel loaded PCL/PEG/PCL thermosensitive hydrogels

作　　者：苗博龙[1] 马桂蕾[1] 宋存先[1] 

机构地区：[1]中国医学科学院北京协和医学院生物医学工程研究所,天津300192

出　　处：《国际生物医学工程杂志》2011年第1期1-4,10,I0006,共6页International Journal of Biomedical Engineering

基　　金：基金项目：国家自然科学基金资助项目（50903093,50873114）;天津市自然科学基金项目（10JCYBJC01700）

摘　　要：目的利用聚己内酯-聚乙二醇-聚己内酯（PCL1250-PEG1500-PCL1250）两亲性聚合物温敏凝胶作为载体材料，构建疏水性抗肿瘤药物紫杉醇的载药体系。方法以辛酸亚锡为催化剂、聚乙二醇为引发剂，引发己内酯单体开环聚合，合成PCL1250-PEG1500-PCL1250三嵌段共聚物。通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行表征；制备不同凝胶浓度及初始载药量的载药温敏凝胶，并对其相转变性能、体外药物释放行为以及体内的生物降解性能进行考察。结果核磁共振及凝胶渗透色谱测定结果表明：合成的共聚物组成与初始投料比一致，符合设计的PCL1250-PEG1500-PCL1250嵌段聚合物结构；该凝胶在15％～30％浓度区间内，具备温敏性溶胶-凝胶相转变能力；该温敏凝胶对紫杉醇具有可控的药物缓释能力，通过改变凝胶浓度及初始载药量可凋节药物释放速率和维持释放的时间。小鼠背部皮下注射PCL1250-PEG1500-PCL1250溶胶后在体内迅速原位凝胶化，凝胶随植入时间逐渐降解至45d时基本降解完全。结论PCL1250-PEG1500-PCL1250温敏凝胶作为紫杉醇载药体系具有良好的药物控释能力和体内生物降解性能。Objective To construct an injectable controlled delivery system of paclitaxel based on thermosensitive PCL1250-PEG1500-PCL1250 hydrogels. Methods A thermosensitive PCL1250-PEG1500-PCL1250 triblock eopolymer was synthesized by ring-opening polymerization of ε-CL using PEG （Mw=1500） as the initiator and Sn（Oet）2 as the catalyst. The synthesized PCL1250-PEG1500-PCL1250 copolymers were characterized for their composition, structure, and molecular weight via LH NMR and GPC techniques. A series of Paclitaxel loaded hydrogels with various predesigned hydrogel concentrations and initial drug loadings were prepared to investigate their gelation ability, in vitro drug release behavior and in vivo biodegradability. Results The results calculated from ^1H NMR and GPC indicated that EG/CL ratio （1.55） was consistent with the initial feed ratio （1.6）, which offered a strong proof to their composition and molecular structure. The thermosensitive PCL1250-PEG1500-PCL1250 hydrogels exhibited a desirable sol-gel transition ability within the concentration range of 15%-30%. The in vitro release rate of paclitaxel from the paclitaxel/PCL1250-PEG1500-PCL1250 hydrogels was controllable by altering the hydrogel concentrations and initial drug loadings. The PCL1250-PEG1500-PCL1250 hydrogels showed a good in situ gelation ability after subcutaneously injected into mouse back. The in situ formed hydrogels gradually degradated with time and almost disappeared after 45 days in vivo. Conclusion Both the controllable drug release behavior and promising biodegradability of this new thermosensitive PCL1250-PEG1500-PCL1250 hydrogels paved a way to develop a novel delivery system for paclitaxel.＇

关 键 词：温敏水凝胶 PCL—PEG—PCL共聚物 紫杉醇 控制释放 生物降解能力 

分 类 号：R318.08[医药卫生—生物医学工程]