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

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%.

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

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 enca...