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紫杉醇PCL—PEG—PCL温敏性缓释凝胶的制备及性能研究
  • ISSN号:1673-4181
  • 期刊名称:《国际生物医学工程杂志》
  • 时间:0
  • 分类:R318.08[医药卫生—生物医学工程;医药卫生—基础医学]
  • 作者机构:[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
  • 相关基金: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)
中文摘要:

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。

英文摘要:

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.'

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期刊信息
  • 《国际生物医学工程杂志》
  • 中国科技核心期刊
  • 主管单位:中华人民共和国国家卫生和计划生育委员会
  • 主办单位:中国医学科学院生物医学工程研究所 中华医学会
  • 主编:
  • 地址:天津市南开区白堤路236号
  • 邮编:300192
  • 邮箱:guobjb@aliyun.com
  • 电话:022-87892617 87893233
  • 国际标准刊号:ISSN:1673-4181
  • 国内统一刊号:ISSN:12-1382/R
  • 邮发代号:18-86
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),中国中国科技核心期刊,中国北大核心期刊(2008版)
  • 被引量:1188