本文主要研究内容
作者吴晓贺（2019）在《两亲性茄呢醇衍生物构建的纳米药物及其抗肿瘤性能研究》一文中研究指出：在纳米载体对难溶性药物的传递中,胶束因具有良好的性能和应用而备受关注。但是在胶束系统中引入大量惰性材料将会出现毒性蓄积和生物代谢等问题。本课题以具备药理活性的茄呢醇为原料,进行茄呢醇衍生物的合成并以此构建纳米载药体系,用于抗肿瘤研究。1.茄呢醇衍生物的合成及胶束制剂性能研究（1）以茄呢醇为原料通过酯化反应、溴代并引入硫醚键等合成SOL-Br、STS、MSS三种茄呢醇衍生物,并以此能制备空白胶束,对4种空白胶束通过激光粒度仪、荧光光度仪、酶标仪等进行CMC测定,储藏、稀释稳定性和溶血率考察,发现修饰后的茄呢醇衍生物比茄呢醇性能有所提高,但是SOL-Br、STS、MSS胶束组存在不能载药等问题,在STS、MSS胶束浓度为10-30μg/mL时溶血率高于5%,但与STS结构相似的对照品FTS符合医用标准。（2）以MTT法将茄呢醇及其衍生物制剂对癌细胞HepG-2、MCF-7、L02进行毒性考察和比较,发现毒性从STS、MSS、SOL-Br、SOL胶束依次减小,而且STS胶束毒性明显高于对照品FTS（48 h时对HepG-2细胞IC50值分别为0.021 mg/mL、0.117mg/mL）,说明制备的茄呢醇衍生物较之茄呢醇其抗肿瘤活性明显增加。2.茄呢醇衍生物与PEG-DiHZ形成载药体系的抗肿瘤研究（1）将PEG进行端基醛基和腙键修饰得到PEG6000-DiCHO和PEG6000-DiHZ,将其作为亲水段与茄呢醇及其衍生物形成自组装体系,首先筛选出只有PEG6000-DiHZ能与茄呢醇衍生物STS、MSS、SOL-Br能形成稳定的载药自组装体系,并以最高载药量为评价标准筛选出两者摩尔比为2:1时获得模型药物阿霉素的载药量分别为3.55%、3.46%、2.91%。（2）按PEG6000-DiHZ与茄呢醇衍生物STS、MSS、SOL-Br摩尔比为2:1时形成空白和载药自组装体,并考察其稳定性、溶血率,不仅解决了单纯茄呢醇衍生物溶血率过高、不能载药等问题,还能证明形成的自组装体具有进一步的静脉给药可行性。（3）载药自组装体体外模拟药物释放实验中3种载药自组装体pH 5.0时,60 h后释放量均达到了75-80%。（4）对空白和载药自组装体进行体外细胞毒性考察,发现对癌细胞抑制结果顺序为Free DOX>STS:PEG6000-DiHZ-DOX>MSS:PEG6000-DiHZ-DOX>SOL-Br:PEG6000-DiHZ-DOX,另外空白自组装体依然保持上一章节中茄呢醇衍生物的细胞毒性,且对癌细胞抑制顺序为STS:PEG6000-DiHZ>MSS:PEG6000-DiHZ>SOL-Br:PEG6000-DiHZ。（5）以H22荷瘤小鼠为模型进行空白及载药自组装体药效学评价,发现抑瘤效果顺序为:STS:PEG6000-DiHZ-DOX>MSS:PEG6000-DiHZ-DOX>SOL-Br:PEG6000-DiHZ-DOX>Free DOX>STS:PEG6000-DiHZ>MSS:PEG6000-DiHZ>SOL-Br:PEG6000-DiHZ;且通过H&E切片及TUNEL结果再次验证了茄呢醇衍生物与药物的联合抗肿瘤效果,并显示出具药理活性的自组装体在纳米医药的良好的应用前景。
Abstract
zai na mi zai ti dui nan rong xing yao wu de chuan di zhong ,jiao shu yin ju you liang hao de xing neng he ying yong er bei shou guan zhu 。dan shi zai jiao shu ji tong zhong yin ru da liang duo xing cai liao jiang hui chu xian du xing xu ji he sheng wu dai xie deng wen ti 。ben ke ti yi ju bei yao li huo xing de jia ne chun wei yuan liao ,jin hang jia ne chun yan sheng wu de ge cheng bing yi ci gou jian na mi zai yao ti ji ,yong yu kang zhong liu yan jiu 。1.jia ne chun yan sheng wu de ge cheng ji jiao shu zhi ji xing neng yan jiu （1）yi jia ne chun wei yuan liao tong guo zhi hua fan ying 、xiu dai bing yin ru liu mi jian deng ge cheng SOL-Br、STS、MSSsan chong jia ne chun yan sheng wu ,bing yi ci neng zhi bei kong bai jiao shu ,dui 4chong kong bai jiao shu tong guo ji guang li du yi 、ying guang guang du yi 、mei biao yi deng jin hang CMCce ding ,chu cang 、xi shi wen ding xing he rong xie lv kao cha ,fa xian xiu shi hou de jia ne chun yan sheng wu bi jia ne chun xing neng you suo di gao ,dan shi SOL-Br、STS、MSSjiao shu zu cun zai bu neng zai yao deng wen ti ,zai STS、MSSjiao shu nong du wei 10-30μg/mLshi rong xie lv gao yu 5%,dan yu STSjie gou xiang shi de dui zhao pin FTSfu ge yi yong biao zhun 。（2）yi MTTfa jiang jia ne chun ji ji yan sheng wu zhi ji dui ai xi bao HepG-2、MCF-7、L02jin hang du xing kao cha he bi jiao ,fa xian du xing cong STS、MSS、SOL-Br、SOLjiao shu yi ci jian xiao ,er ju STSjiao shu du xing ming xian gao yu dui zhao pin FTS（48 hshi dui HepG-2xi bao IC50zhi fen bie wei 0.021 mg/mL、0.117mg/mL）,shui ming zhi bei de jia ne chun yan sheng wu jiao zhi jia ne chun ji kang zhong liu huo xing ming xian zeng jia 。2.jia ne chun yan sheng wu yu PEG-DiHZxing cheng zai yao ti ji de kang zhong liu yan jiu （1）jiang PEGjin hang duan ji quan ji he zong jian xiu shi de dao PEG6000-DiCHOhe PEG6000-DiHZ,jiang ji zuo wei qin shui duan yu jia ne chun ji ji yan sheng wu xing cheng zi zu zhuang ti ji ,shou xian shai shua chu zhi you PEG6000-DiHZneng yu jia ne chun yan sheng wu STS、MSS、SOL-Brneng xing cheng wen ding de zai yao zi zu zhuang ti ji ,bing yi zui gao zai yao liang wei ping jia biao zhun shai shua chu liang zhe ma er bi wei 2:1shi huo de mo xing yao wu a mei su de zai yao liang fen bie wei 3.55%、3.46%、2.91%。（2）an PEG6000-DiHZyu jia ne chun yan sheng wu STS、MSS、SOL-Brma er bi wei 2:1shi xing cheng kong bai he zai yao zi zu zhuang ti ,bing kao cha ji wen ding xing 、rong xie lv ,bu jin jie jue le chan chun jia ne chun yan sheng wu rong xie lv guo gao 、bu neng zai yao deng wen ti ,hai neng zheng ming xing cheng de zi zu zhuang ti ju you jin yi bu de jing mai gei yao ke hang xing 。（3）zai yao zi zu zhuang ti ti wai mo ni yao wu shi fang shi yan zhong 3chong zai yao zi zu zhuang ti pH 5.0shi ,60 hhou shi fang liang jun da dao le 75-80%。（4）dui kong bai he zai yao zi zu zhuang ti jin hang ti wai xi bao du xing kao cha ,fa xian dui ai xi bao yi zhi jie guo shun xu wei Free DOX>STS:PEG6000-DiHZ-DOX>MSS:PEG6000-DiHZ-DOX>SOL-Br:PEG6000-DiHZ-DOX,ling wai kong bai zi zu zhuang ti yi ran bao chi shang yi zhang jie zhong jia ne chun yan sheng wu de xi bao du xing ,ju dui ai xi bao yi zhi shun xu wei STS:PEG6000-DiHZ>MSS:PEG6000-DiHZ>SOL-Br:PEG6000-DiHZ。（5）yi H22he liu xiao shu wei mo xing jin hang kong bai ji zai yao zi zu zhuang ti yao xiao xue ping jia ,fa xian yi liu xiao guo shun xu wei :STS:PEG6000-DiHZ-DOX>MSS:PEG6000-DiHZ-DOX>SOL-Br:PEG6000-DiHZ-DOX>Free DOX>STS:PEG6000-DiHZ>MSS:PEG6000-DiHZ>SOL-Br:PEG6000-DiHZ;ju tong guo H&Eqie pian ji TUNELjie guo zai ci yan zheng le jia ne chun yan sheng wu yu yao wu de lian ge kang zhong liu xiao guo ,bing xian shi chu ju yao li huo xing de zi zu zhuang ti zai na mi yi yao de liang hao de ying yong qian jing 。
论文参考文献
论文详细介绍
论文作者分别是来自河南大学的吴晓贺，发表于刊物河南大学2019-09-20论文，是一篇关于茄呢醇衍生物论文,腙化论文,自组装论文,纳米胶束论文,阿霉素论文,联合抗肿瘤论文,河南大学2019-09-20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，资料来自河南大学2019-09-20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：茄呢醇衍生物论文; 腙化论文; 自组装论文; 纳米胶束论文; 阿霉素论文; 联合抗肿瘤论文; 河南大学2019-09-20论文;