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(英文)  

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

作　　者：田志立[1] 吴尧[1] 刘荣[1] 肖严峰[1] 何斌[1] 顾忠伟[1] 吴方[1] 

机构地区：[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

出　　处：《中国组织工程研究与临床康复》2011年第29期5501-5506,共6页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：the State High-Tech Research and Development Plans of China,No.2006AA02A135~~

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1HNMR,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,12h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7d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50~100μm之间。鼠成纤维细胞与浓度为100%的凝胶浸提液共培养72h之后,细胞的存活率为99.3%。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 fibr

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 

分 类 号：R318.08[医药卫生—生物医学工程]