本文主要研究内容
作者杨波（2019）在《两种水溶性硫化氢供体纳米粒的制备及抗肿瘤研究》一文中研究指出：目前纳米载药系统已被广泛应用于难溶性药物在生物体内的递送,它们能增加难溶性药物水溶性和稳定性,在一定程度上使难溶性药物的生物相容性得到了改善。本文制备了两种纳米载药材料,分别是以聚乙二醇和格尔伯特十六醇为材料制备的载药胶束和以透明质酸为载体制备的载药纳米粒。两个递送系统用于增加难溶性药物硫化氢供体ADT-OH和姜黄素的水溶性,以改善药物作用效果和联合给药能力。（1）还原敏感性格尔伯特十六醇胶束的制备及抗癌药物的递送将二硫代二丙酸与格尔伯特十六醇进行单端的酯化,制备二硫代二丙酸格尔伯特十六醇单酯G16SS,利用G16SS中二硫代二丙酸的另一个羧基与聚乙二醇单甲醚酯化后得到具有还原敏感性的胶束材料G16MPGS;利用甘氨酸为中间体将聚乙二醇单甲醚羧基化随即与格尔伯特十六醇进行酯化反应制备出G16MPG胶束材料。以难溶性硫化氢供体ADT-OH为目标药物,利用溶剂挥发法将两种材料负载ADT-OH制备出载药胶束G16MPGS-ADT和G16MPG-ADT;并对两种载药胶束进行形貌,载药量,体外释放和稳定性表征。表征结果显示载药胶束的粒径均小于200 nm,PDI较小0.10.2,分布均匀;载药胶束在被稀释和室温长久放置后粒径依然相对稳定;胶束的载药量都大于4.3%;体外释放结果显示,在GSH环境作用下,药物能快速地释放。体外考察载药胶束细胞毒性和血液安全性结果显示两种空白胶束对肿瘤细胞和正常细胞均无明显的毒性;相比于游离药物,载药胶束显示出优异的体外肿瘤细胞生长抑制作用,具有还原敏感性的载药胶束G16MPGS-ADT作用效果要优于普通载药胶束G16MPG-ADT;细胞凋亡实验结果显示,载药胶束促进肿瘤细胞凋亡且呈浓度依赖性,这一结果与MTT结果相符合;体外溶血实验结果显示空白胶束和载药胶束对大鼠的红细胞溶血率均低于5.0%的上限值,符合静脉注射给药的要求。我们构建H22荷瘤小鼠模型考察了载药胶束体内药效学;实验结果显示在给药相同的时间内两种载药胶束对肿瘤生长的抑制作用均优于游离药物,而具有还原敏感性的G16MPGS-ADT胶束作用效果明显大于G16MPG-ADT胶束;H&E切片结果显示,两种载药胶束作用后肿瘤组织都出现较对照组多的细胞坏死区域但并未对小鼠的肝脏及心脏组织造成损伤。实验证明,我们利用格尔伯特十六醇成功地制备出了安全可靠,具有还原敏感性的胶束材料并且能较好地负载硫化氢供体ADT-OH药物;体内外实验结果表明,我们所制备的载药胶束在抑制肿瘤细胞增殖中具有突出的作用。（2）透明质酸分别接枝ADT-OH和姜黄素纳米粒的制备及联合用药在本研究中,我们利用水溶性透明质酸（HA）作为药物载体材料,通过化学反应分别制备了透明质酸的姜黄素接枝物（HA-Cur）和透明质酸的ADT-OH接枝物（HA-ADT）,让两种接枝物在水中自组装形成载药纳米粒;利用核磁氢谱检测计算药物接枝率,体外考察两种纳米粒的粒径,药物的存在状态及释放情况;实验结果显示两种纳米药物的药物接枝率分别为HA-Cur 7.0%和ADT-OH 18.0%,两种纳米粒的粒径均在250-260 nm之间;DSC结果显示两种药物在纳米粒子中都是以无定型状态存在,进一步说明两种药物成功地接枝到透明质酸上;体外释放结果显示48小时内HA-Cur的累积释放量超过40%,HA-ADT的释放量累积超过30%。选择人肝癌细胞7721,乳腺癌细胞MB-MDA-231和MCF-7三种细胞表面过表达CD44受体的肿瘤细胞,进行了两种纳米药物的体外细胞毒性实验和细胞增殖实验（EDU）,实验结果显示HA-Cur、HA-ADT纳米粒对所选肿瘤细胞的增长抑制作用均好于游离药物,联合用药优于单独给药;肿瘤细胞EDU实验结果显示药物纳米粒组的细胞增殖较游离药物的少,联合给药组较单独给药组少,这一结果与细胞毒性MTT实验结果一致。两种纳米粒的体外溶血实验结果表明,溶血率都小于4%,说明药物可用于注射给药。构建小鼠肝癌实体瘤模型评估纳米粒联合给药体内抑制肿瘤生长情况;实验结果显示相同的给药周期内联合给药组对肿瘤生长抑制更为明显,小鼠体重几乎没有变化可以证明药物对小鼠没有毒性或毒性较低。通过以上实验结果我们得出透明质酸修饰后的两种难溶性药物体内外的抗肿瘤效果都好于游离药物,而联合用药效果好于单独给药。
Abstract
mu qian na mi zai yao ji tong yi bei an fan ying yong yu nan rong xing yao wu zai sheng wu ti nei de di song ,ta men neng zeng jia nan rong xing yao wu shui rong xing he wen ding xing ,zai yi ding cheng du shang shi nan rong xing yao wu de sheng wu xiang rong xing de dao le gai shan 。ben wen zhi bei le liang chong na mi zai yao cai liao ,fen bie shi yi ju yi er chun he ge er bai te shi liu chun wei cai liao zhi bei de zai yao jiao shu he yi tou ming zhi suan wei zai ti zhi bei de zai yao na mi li 。liang ge di song ji tong yong yu zeng jia nan rong xing yao wu liu hua qing gong ti ADT-OHhe jiang huang su de shui rong xing ,yi gai shan yao wu zuo yong xiao guo he lian ge gei yao neng li 。（1）hai yuan min gan xing ge er bai te shi liu chun jiao shu de zhi bei ji kang ai yao wu de di song jiang er liu dai er bing suan yu ge er bai te shi liu chun jin hang chan duan de zhi hua ,zhi bei er liu dai er bing suan ge er bai te shi liu chun chan zhi G16SS,li yong G16SSzhong er liu dai er bing suan de ling yi ge suo ji yu ju yi er chun chan jia mi zhi hua hou de dao ju you hai yuan min gan xing de jiao shu cai liao G16MPGS;li yong gan an suan wei zhong jian ti jiang ju yi er chun chan jia mi suo ji hua sui ji yu ge er bai te shi liu chun jin hang zhi hua fan ying zhi bei chu G16MPGjiao shu cai liao 。yi nan rong xing liu hua qing gong ti ADT-OHwei mu biao yao wu ,li yong rong ji hui fa fa jiang liang chong cai liao fu zai ADT-OHzhi bei chu zai yao jiao shu G16MPGS-ADThe G16MPG-ADT;bing dui liang chong zai yao jiao shu jin hang xing mao ,zai yao liang ,ti wai shi fang he wen ding xing biao zheng 。biao zheng jie guo xian shi zai yao jiao shu de li jing jun xiao yu 200 nm,PDIjiao xiao 0.10.2,fen bu jun yun ;zai yao jiao shu zai bei xi shi he shi wen chang jiu fang zhi hou li jing yi ran xiang dui wen ding ;jiao shu de zai yao liang dou da yu 4.3%;ti wai shi fang jie guo xian shi ,zai GSHhuan jing zuo yong xia ,yao wu neng kuai su de shi fang 。ti wai kao cha zai yao jiao shu xi bao du xing he xie ye an quan xing jie guo xian shi liang chong kong bai jiao shu dui zhong liu xi bao he zheng chang xi bao jun mo ming xian de du xing ;xiang bi yu you li yao wu ,zai yao jiao shu xian shi chu you yi de ti wai zhong liu xi bao sheng chang yi zhi zuo yong ,ju you hai yuan min gan xing de zai yao jiao shu G16MPGS-ADTzuo yong xiao guo yao you yu pu tong zai yao jiao shu G16MPG-ADT;xi bao diao wang shi yan jie guo xian shi ,zai yao jiao shu cu jin zhong liu xi bao diao wang ju cheng nong du yi lai xing ,zhe yi jie guo yu MTTjie guo xiang fu ge ;ti wai rong xie shi yan jie guo xian shi kong bai jiao shu he zai yao jiao shu dui da shu de gong xi bao rong xie lv jun di yu 5.0%de shang xian zhi ,fu ge jing mai zhu she gei yao de yao qiu 。wo men gou jian H22he liu xiao shu mo xing kao cha le zai yao jiao shu ti nei yao xiao xue ;shi yan jie guo xian shi zai gei yao xiang tong de shi jian nei liang chong zai yao jiao shu dui zhong liu sheng chang de yi zhi zuo yong jun you yu you li yao wu ,er ju you hai yuan min gan xing de G16MPGS-ADTjiao shu zuo yong xiao guo ming xian da yu G16MPG-ADTjiao shu ;H&Eqie pian jie guo xian shi ,liang chong zai yao jiao shu zuo yong hou zhong liu zu zhi dou chu xian jiao dui zhao zu duo de xi bao huai si ou yu dan bing wei dui xiao shu de gan zang ji xin zang zu zhi zao cheng sun shang 。shi yan zheng ming ,wo men li yong ge er bai te shi liu chun cheng gong de zhi bei chu le an quan ke kao ,ju you hai yuan min gan xing de jiao shu cai liao bing ju neng jiao hao de fu zai liu hua qing gong ti ADT-OHyao wu ;ti nei wai shi yan jie guo biao ming ,wo men suo zhi bei de zai yao jiao shu zai yi zhi zhong liu xi bao zeng shi zhong ju you tu chu de zuo yong 。（2）tou ming zhi suan fen bie jie zhi ADT-OHhe jiang huang su na mi li de zhi bei ji lian ge yong yao zai ben yan jiu zhong ,wo men li yong shui rong xing tou ming zhi suan （HA）zuo wei yao wu zai ti cai liao ,tong guo hua xue fan ying fen bie zhi bei le tou ming zhi suan de jiang huang su jie zhi wu （HA-Cur）he tou ming zhi suan de ADT-OHjie zhi wu （HA-ADT）,rang liang chong jie zhi wu zai shui zhong zi zu zhuang xing cheng zai yao na mi li ;li yong he ci qing pu jian ce ji suan yao wu jie zhi lv ,ti wai kao cha liang chong na mi li de li jing ,yao wu de cun zai zhuang tai ji shi fang qing kuang ;shi yan jie guo xian shi liang chong na mi yao wu de yao wu jie zhi lv fen bie wei HA-Cur 7.0%he ADT-OH 18.0%,liang chong na mi li de li jing jun zai 250-260 nmzhi jian ;DSCjie guo xian shi liang chong yao wu zai na mi li zi zhong dou shi yi mo ding xing zhuang tai cun zai ,jin yi bu shui ming liang chong yao wu cheng gong de jie zhi dao tou ming zhi suan shang ;ti wai shi fang jie guo xian shi 48xiao shi nei HA-Curde lei ji shi fang liang chao guo 40%,HA-ADTde shi fang liang lei ji chao guo 30%。shua ze ren gan ai xi bao 7721,ru xian ai xi bao MB-MDA-231he MCF-7san chong xi bao biao mian guo biao da CD44shou ti de zhong liu xi bao ,jin hang le liang chong na mi yao wu de ti wai xi bao du xing shi yan he xi bao zeng shi shi yan （EDU）,shi yan jie guo xian shi HA-Cur、HA-ADTna mi li dui suo shua zhong liu xi bao de zeng chang yi zhi zuo yong jun hao yu you li yao wu ,lian ge yong yao you yu chan du gei yao ;zhong liu xi bao EDUshi yan jie guo xian shi yao wu na mi li zu de xi bao zeng shi jiao you li yao wu de shao ,lian ge gei yao zu jiao chan du gei yao zu shao ,zhe yi jie guo yu xi bao du xing MTTshi yan jie guo yi zhi 。liang chong na mi li de ti wai rong xie shi yan jie guo biao ming ,rong xie lv dou xiao yu 4%,shui ming yao wu ke yong yu zhu she gei yao 。gou jian xiao shu gan ai shi ti liu mo xing ping gu na mi li lian ge gei yao ti nei yi zhi zhong liu sheng chang qing kuang ;shi yan jie guo xian shi xiang tong de gei yao zhou ji nei lian ge gei yao zu dui zhong liu sheng chang yi zhi geng wei ming xian ,xiao shu ti chong ji hu mei you bian hua ke yi zheng ming yao wu dui xiao shu mei you du xing huo du xing jiao di 。tong guo yi shang shi yan jie guo wo men de chu tou ming zhi suan xiu shi hou de liang chong nan rong xing yao wu ti nei wai de kang zhong liu xiao guo dou hao yu you li yao wu ,er lian ge yong yao xiao guo hao yu chan du gei yao 。
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论文作者分别是来自河南大学的杨波，发表于刊物河南大学2019-09-20论文，是一篇关于格尔伯特醇论文,聚合物胶束论文,硫化氢供体论文,透明质酸论文,姜黄素论文,联合给药论文,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：格尔伯特醇论文; 聚合物胶束论文; 硫化氢供体论文; 透明质酸论文; 姜黄素论文; 联合给药论文; 河南大学2019-09-20论文;