CAJ | 학술논문

考察了温敏性PCL-PEG-PCL水凝胶中聚乙二醇(PEG)及聚己内酯(PCL)不同嵌段组成对其溶胶-凝胶相转变温度以及亲水性药物(牛血清白蛋白,BSA)释放速率的影响.采用开环聚合法,以辛酸亚锡为催化剂、PEG1500/PEG1000为引发剂,与己内酯单体发生开环共聚,合成了一系列具有不同PEG和PCL嵌段长度的PCL-PEG-PCL型三嵌段共聚物.通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行了表征.共聚物的溶胶-凝胶相变温度由翻转试管法测定.利用透射电镜、核磁共振氢谱及荧光探针技术证实了该材料在水溶液中胶束的形成.以BSA为模型蛋白药物,制备载药水凝胶,利用microBCA法测定药物在释放介质中的浓度,研究其体外释放行为.实验结果表明,共聚物的溶胶-凝胶相变温度与PCL及PEG嵌段长度紧密相关,即在给定共聚物浓度情况下,固定PEG嵌段长度而增加PCL嵌段长度,会导致相变温度降低;而固定PCL嵌段长度而增加PEG嵌段长度,其相变温度相应升高.水凝胶中蛋白药物的释放速率与疏水的PCL嵌段长度无关,而与亲水的PEG嵌段长度密切相关,即PEG嵌段越长,蛋白药物释放越快.
고찰료온민성PCL-PEG-PCL수응효중취을이순(PEG)급취기내지(PCL)불동감단조성대기용효-응효상전변온도이급친수성약물(우혈청백단백,BSA)석방속솔적영향.채용개배취합법,이신산아석위최화제、PEG1500/PEG1000위인발제,여기내지단체발생개배공취,합성료일계렬구유불동PEG화PCL감단장도적PCL-PEG-PCL형삼감단공취물.통과핵자공진경보급응효삼투색보대기조성、결구급분자량진행료표정.공취물적용효-응효상변온도유번전시관법측정.이용투사전경、핵자공진경보급형광탐침기술증실료해재료재수용액중효속적형성.이BSA위모형단백약물,제비재약수응효,이용microBCA법측정약물재석방개질중적농도,연구기체외석방행위.실험결과표명,공취물적용효-응효상변온도여PCL급PEG감단장도긴밀상관,즉재급정공취물농도정황하,고정PEG감단장도이증가PCL감단장도,회도치상변온도강저;이고정PCL감단장도이증가PEG감단장도,기상변온도상응승고.수응효중단백약물적석방속솔여소수적PCL감단장도무관,이여친수적PEG감단장도밀절상관,즉PEG감단월장,단백약물석방월쾌.
The effect of PEG and PCL composition of thermosensitive PCL-PEG-PCL hydrogels on Sol-gel transition temperature and release rate of bovine serum albumin (BSA) were investigated. A series of thermosensitive PCL-PEG-PCL triblock copolymers with different PEG and PCL block lengths were synthesized via ring-opening polymerization of ε-CL using PEG1500/PEG1000 as the initiator and Sn( Oct)_2 as the catalyst.Their composition, structure, and molecular weight were characterized via ~1H NMR and GPC techniques. The Sol-gel transition temperature was determined with the test tube inverting method. TEM, ~1H NMR, and fluorescence probe technique were employed to identify formation of micelles of the triblock copolymers in aqueous solution. BSA was used as a model protein drug. Hydrogels of these PCL-PEG-PCL triblock copolymers loaded with BSA were prepared for in vitro release study, and BSA concentration in the released sample was determined with microBCA method. The effect of PCL and PEG block lengths on Sol-gel transition temperature and release rate of BSA was also discussed. The results obtained indicated that the Sol-gel transition temperature of copolymers was related to block lengths of PCL and PEG, increasing the PCL length at a fixed PEG central block led to a lower transition temperature at a given copolymer concentration, while with the enhancement of the PEG length at a similar hydrophobic PCL length, the transition temperature increases. And the protein release rate was independent of the hydrophobic PCL length, whereas the longer PEG length, the lower protein release rate.