中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (29): 5501-5506.doi: 10.3969/j.issn.1673-8225.2011.29.045

• 药物控释材料 drug delivery materials • 上一篇    下一篇

对映异构聚乳酸/聚乙二醇空间异构复合水凝胶的药物释放及形貌和细胞毒性

田志立，吴  尧，刘  荣，肖严峰，何  斌，顾忠伟，吴  方   

  1. 四川大学国家生物医用材料工程技术研究中心，四川省成都市  610064
  • 收稿日期:2010-11-18 修回日期:2011-02-14 出版日期:2011-07-16 发布日期:2011-07-16
  • 通讯作者: 何斌，教授，四川大学国家生物医用材料工程技术研究中心，四川省成都市 610064 并列通讯作者：吴方，教授，四川大学国家生物医用材料工程技术研究中心，四川省成都市 610064
  • 作者简介:田志立★，女，1985年生，云南省大理白族自治州人，白族，四川大学在读硕士，主要从事生物活性水凝胶及药物释放的研究。
  • 基金资助:

    国家高技术研究发展计划(2006AA02A135)“新型人工关节的研制与应用”。

Drug release, morphology and cytotoxicity of enantiomeric poly(L-Lactic acid)-poly(ethylene glycol)-poly(L-Lactic acid)/poly(D-Lactic acid)-poly(ethylene glycol)- poly(D-Lactic acid) stereocomplex hydrogel

Tian Zhi-li, Wu Yao, Liu Rong, Xiao Yan-feng, He Bin, Gu Zhong-wei, Wu Fang   

  1. National Engineering Research Center for Biomaterials, Sichuan University, Chengdu  610064, Sichuan Province, China
  • Received:2010-11-18 Revised:2011-02-14 Online:2011-07-16 Published:2011-07-16
  • Contact: He Bin, Professor, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan Province, China bhe@scu.edu.cn Correspondence to: Wu Fang, Professor, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan Province, China fangwu0808@yahoo.com, fwu@scu.edu.cn
  • About author:Tian Zhi-li★, Studying for master’s degree, National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan Province, China tianzhili541@126.com
  • Supported by:

    the State High-Tech Research and Development Plans of China, No. 2006AA02A135*

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摘要：

背景：目前生物降解水凝胶已被广泛应用于抗癌药物及生物活性大分子的装载，但为了保护生物活性大分子的活性，需要得到凝胶化条件更温和，凝胶化时间更短的凝胶体系。
目的：制备对映异构聚乳酸∕聚乙二醇的空间异构复合水凝胶，使其具有更短的凝胶化时间，实现对模拟药物溶菌酶的装载和控释。
方法：以聚乙二醇为引发剂，辛酸亚锡为催化剂，丙交酯与聚乙二醇发生开环聚合反应，得到聚乳酸/聚乙二醇的三嵌段共聚物(PLLA-PEG-PLLA 和 PDLA-PEG-PDLA)。用1H NMR，FT-IR 和 XRD表征三嵌段共聚物。10% PLLA20-PEG227-PLLA20的水溶液和10%PDLA21-PEG227-PDLA21的水溶液在室温下混合，12 h后形成凝胶。通过XRD考察凝胶化机制，以溶菌酶为模拟药物，考察凝胶的释药特性，通过扫描电镜考察凝胶的形貌，采用MTT法考察凝胶的细胞毒性。
结果与结论：成功得到聚乳酸/聚乙二醇的三嵌段共聚物，在嵌段共聚物中，聚乳酸嵌段和聚乙二醇嵌段都能结晶，但以聚乙二醇嵌段的结晶为主。通过XRD证明凝胶中存在空间异构复合作用，溶菌酶在凝胶中通过凝胶的溶蚀和降解行为，在7 d之内释放完全。通过扫描电镜观察到冻干的水凝胶呈三维贯穿的多孔结构，空隙尺寸在50~100 μm 之间。鼠成纤维细胞与浓度为100%的凝胶浸提液共培养72 h之后，细胞的存活率为99.3%。

关键词: 水凝胶, 空间异构复合作用, 药物载体, 共聚物, 细胞毒性

Abstract:

BACKGROUND: Recently biodegradable hydrogel has been extensively used to delivery anticancer drug and bioactive macromolecule. However, to protect the activity of the bioactive macromolecule, we need to obtain series of hydrogel which have milder hydrogelation conditions and shorter hydroglation time.
OBJECTIVE: To prepare enantiomeric poly(L-Lactic acid) (PLLA)-poly(ethylene glycol (PEG)-PLLA/ poly(D-Lactic acid) (PDLA)-PEG-PDLA stereocomplex hydrogel which has shorter hydroglation time, to physically encapsulate a model drug-lysozyme and sustained release it from the hydrogel.
METHODS: Triblock copolymers of PLLA-PEG-PLLA and PDLA-PEG-PDLA were synthesized by ring-opening polymerization of L(D)-lactide using PEG as the initiator and Sn(Oct)2 as the catalyst. The triblock copolymers were characterized by 1H nuclear magnetic resonance, FT-IR and X-Ray diffractometry. A hydrogel was prepared from an aqueous mixture of PLLA20-PEG227-PLLA20 and PDLA21-PEG227-PDLA21 (10 wt% concentration) at room temperature for 12 hours. X-Ray diffractometry test was used to research the gelation mechanism. The release profile of the lysozyme as a model drug from the hydrogel was tested. The morphology of the freeze-dried hydrogel was investigated by scanning electron microscope. The cytotoxicity of the hydrogel was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide) assay.
RESULTS AND CONCLUSION: Triblock copolymers of PLLA-PEG-PLLA and PDLA-PEG-PDLA were obtained. Both the PEG and PLA blocks in the copolymers could crystallize, but the crystallization of the PEG block was predominant. The stereocomplex formation between the PLLA and PDLA blocks within the hydrogel was confirmed by the X-Ray diffractometry analysis. The release profile of the lysozyme from the hydrogel exhibited a sustained-release pattern with a duration period of 7 days. The hydrogel exhibited a 3D interconnected porous structure with 50-100 μm pore size after being freeze-dried. The mouse fibroblast cell viability percentage was 99.3% after the cells contacted with the 100% extracted liquid for 72 hours.

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