本文主要研究内容
作者李荣烨(2019)在《聚乙二醇-聚乳酸-聚乙二醇三嵌段共聚物囊泡药物缓释体系的研究》一文中研究指出:当今,随着医药迅速发展,可降解高分子聚合物已广泛应用于生物医用材料,其具有很好的生物相容性和体内可降解性,因而成为研究人员广泛关注的焦点。聚乳酸(PLA)和聚乙二醇(PEG)的共聚物已用于生物医学工程,包括手术缝合线、心脏封堵器、骨支架、药物缓控释载体和组织工程支架等。近几年,研究者们对由两亲性三嵌段共聚物自组装形成的囊泡药物缓释体系进行了广泛的研究。由于囊泡具有高通透性和滞留效应(EPR效应),在肿瘤部位可以实现高浓度积累,同时满足体内长循环的要求。囊泡具有“亲水-疏水-亲水”三层结构,因此可同时包载亲、疏水两种水溶性不同的药物。因此,研究两亲性三嵌段共聚物囊泡的药物缓释并将其应用于癌症治疗具有很大的临床价值和意义。本文以mPEG为引发剂,在辛酸亚锡的催化下通过丙交酯开环聚合反应得到PEG-PLA二嵌段共聚物,PEG-PLA二嵌段共聚物末端炔烃化后再与PEG-N3反应得到PEG-PLA-PEG三嵌段共聚物。利用1H NMR、GPC等方法研究了三嵌段共聚物的组成及结构、分子量及热力学性质等。通过共溶剂蒸发法制备囊泡,借助TEM、DLS等观察囊泡的形态和尺寸。本课题选用两种水溶性不同的药物,疏水性紫杉醇和亲水性顺铂,利用透析法进行载药,三嵌段共聚物囊泡的包封率、载药量以及载药后的药物释放通过高效液相色谱法(HPLC)和电感耦合等离子体光谱法(ICP)测试。为了检验所合成三嵌段共聚物材料的毒性,进行了细胞相容性、血液相容性以及斑马鱼胚胎毒性实验,根据一系列实验数据来评价其生物相容性。对PEG-PLA-PEG三嵌段共聚物囊泡进行了体外降解实验,使用磷酸盐缓冲溶液模拟体内环境,通过透射电镜(TEM)、粒径(DLS)和凝胶渗透色谱(GPC)等一系列表征手段,研究三嵌段共聚物材料的降解行为。综上得出以下结论,PEG-PLA-PEG三嵌段共聚物通过共溶剂蒸发法自组装形成囊泡,载药性能较好,且包封率和载药量较高,药物释放曲线趋于平稳。囊泡具有较好的生物相容性,无论是细胞、血液相容性评价,还是斑马鱼胚胎毒性实验,都指示该自组装形成的囊泡是比较理想的临床药物缓释体系。同时,囊泡载药体系两种药物的载药量和包封率都比较高,药物在一周内的释放曲线较平稳,没有明显的突释现象。另外,当疏水段的长度较短时,疏水性药物释放速率较快。降解实验显示三嵌段共聚物囊泡在45天时降解较完全,PLA疏水链段降解时间取决于链段的长度,如果PLA链段比例较高,则降解时间延长,结构崩解趋于缓慢。
Abstract
dang jin ,sui zhao yi yao xun su fa zhan ,ke jiang jie gao fen zi ju ge wu yi an fan ying yong yu sheng wu yi yong cai liao ,ji ju you hen hao de sheng wu xiang rong xing he ti nei ke jiang jie xing ,yin er cheng wei yan jiu ren yuan an fan guan zhu de jiao dian 。ju ru suan (PLA)he ju yi er chun (PEG)de gong ju wu yi yong yu sheng wu yi xue gong cheng ,bao gua shou shu feng ge xian 、xin zang feng du qi 、gu zhi jia 、yao wu huan kong shi zai ti he zu zhi gong cheng zhi jia deng 。jin ji nian ,yan jiu zhe men dui you liang qin xing san qian duan gong ju wu zi zu zhuang xing cheng de nang pao yao wu huan shi ti ji jin hang le an fan de yan jiu 。you yu nang pao ju you gao tong tou xing he zhi liu xiao ying (EPRxiao ying ),zai zhong liu bu wei ke yi shi xian gao nong du ji lei ,tong shi man zu ti nei chang xun huan de yao qiu 。nang pao ju you “qin shui -shu shui -qin shui ”san ceng jie gou ,yin ci ke tong shi bao zai qin 、shu shui liang chong shui rong xing bu tong de yao wu 。yin ci ,yan jiu liang qin xing san qian duan gong ju wu nang pao de yao wu huan shi bing jiang ji ying yong yu ai zheng zhi liao ju you hen da de lin chuang jia zhi he yi yi 。ben wen yi mPEGwei yin fa ji ,zai xin suan ya xi de cui hua xia tong guo bing jiao zhi kai huan ju ge fan ying de dao PEG-PLAer qian duan gong ju wu ,PEG-PLAer qian duan gong ju wu mo duan gui ting hua hou zai yu PEG-N3fan ying de dao PEG-PLA-PEGsan qian duan gong ju wu 。li yong 1H NMR、GPCdeng fang fa yan jiu le san qian duan gong ju wu de zu cheng ji jie gou 、fen zi liang ji re li xue xing zhi deng 。tong guo gong rong ji zheng fa fa zhi bei nang pao ,jie zhu TEM、DLSdeng guan cha nang pao de xing tai he che cun 。ben ke ti shua yong liang chong shui rong xing bu tong de yao wu ,shu shui xing zi sha chun he qin shui xing shun bo ,li yong tou xi fa jin hang zai yao ,san qian duan gong ju wu nang pao de bao feng lv 、zai yao liang yi ji zai yao hou de yao wu shi fang tong guo gao xiao ye xiang se pu fa (HPLC)he dian gan ou ge deng li zi ti guang pu fa (ICP)ce shi 。wei le jian yan suo ge cheng san qian duan gong ju wu cai liao de du xing ,jin hang le xi bao xiang rong xing 、xie ye xiang rong xing yi ji ban ma yu pei tai du xing shi yan ,gen ju yi ji lie shi yan shu ju lai ping jia ji sheng wu xiang rong xing 。dui PEG-PLA-PEGsan qian duan gong ju wu nang pao jin hang le ti wai jiang jie shi yan ,shi yong lin suan yan huan chong rong ye mo ni ti nei huan jing ,tong guo tou she dian jing (TEM)、li jing (DLS)he ning jiao shen tou se pu (GPC)deng yi ji lie biao zheng shou duan ,yan jiu san qian duan gong ju wu cai liao de jiang jie hang wei 。zeng shang de chu yi xia jie lun ,PEG-PLA-PEGsan qian duan gong ju wu tong guo gong rong ji zheng fa fa zi zu zhuang xing cheng nang pao ,zai yao xing neng jiao hao ,ju bao feng lv he zai yao liang jiao gao ,yao wu shi fang qu xian qu yu ping wen 。nang pao ju you jiao hao de sheng wu xiang rong xing ,mo lun shi xi bao 、xie ye xiang rong xing ping jia ,hai shi ban ma yu pei tai du xing shi yan ,dou zhi shi gai zi zu zhuang xing cheng de nang pao shi bi jiao li xiang de lin chuang yao wu huan shi ti ji 。tong shi ,nang pao zai yao ti ji liang chong yao wu de zai yao liang he bao feng lv dou bi jiao gao ,yao wu zai yi zhou nei de shi fang qu xian jiao ping wen ,mei you ming xian de tu shi xian xiang 。ling wai ,dang shu shui duan de chang du jiao duan shi ,shu shui xing yao wu shi fang su lv jiao kuai 。jiang jie shi yan xian shi san qian duan gong ju wu nang pao zai 45tian shi jiang jie jiao wan quan ,PLAshu shui lian duan jiang jie shi jian qu jue yu lian duan de chang du ,ru guo PLAlian duan bi li jiao gao ,ze jiang jie shi jian yan chang ,jie gou beng jie qu yu huan man 。
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论文作者分别是来自青岛科技大学的李荣烨,发表于刊物青岛科技大学2019-07-19论文,是一篇关于囊泡论文,两亲性三嵌段共聚物论文,药物缓释体系论文,自组装论文,抗癌药物论文,生物相容性论文,青岛科技大学2019-07-19论文的文章。本文可供学术参考使用,各位学者可以免费参考阅读下载,文章观点不代表本站观点,资料来自青岛科技大学2019-07-19论文网站,若本站收录的文献无意侵犯了您的著作版权,请联系我们删除。
标签:囊泡论文; 两亲性三嵌段共聚物论文; 药物缓释体系论文; 自组装论文; 抗癌药物论文; 生物相容性论文; 青岛科技大学2019-07-19论文;