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作者毛丽燕（2019）在《多西他赛靶向纳米粒的构建及其抗肿瘤作用研究》一文中研究指出：目前,由于生活压力加大以及环境恶化等因素癌症发病率不断上升,癌症已成为我国主要死亡原因之一。手术切除、放射治疗和化学治疗是目前治疗癌症的主要手段,但都存在一定的局限性。为了改善化疗药物的问题,新型药物递送系统的研究是抗肿瘤药物的研究热点。纳米药物递送系统可采用生物降解性良好的材料提高药物溶解度,提高靶向性减少对其他组织的损害。目的:多西他赛,紫杉烷类半合成抗肿瘤药物,微管蛋白抑制剂。本文以多西他赛为主药,以卵磷脂为载体材料,使用O/W乳化溶剂挥发法制备纳米粒,十八胺为正电荷调节剂,采用DSPE-PEG2000进行纳米粒修饰,β-灵芝葡聚糖利用正负电荷吸附作用包覆在正电荷纳米粒表面,Zeta电位测定可知灵芝多糖吸附多西他赛纳米粒带负电。对纳米粒的包封率、载药量、粒径及其Zeta电位进行表征。以多西他赛市售制剂为对照,考察纳米粒的体外释放和稳定性,评价纳米粒对肿瘤细胞的细胞毒作用和荷瘤小鼠的体内抑瘤效果,为纳米粒的下一步研究提供理论上的指导。方法:本实验通过O/W乳化溶剂挥发法制备了多西他赛纳米粒,建立了高效液相色谱法测定多西他赛纳米粒含量测定方法,流动相为乙腈︰水=55︰45,流速为1.0m L/min,确定紫外检测波长为230 nm。进行方法学验证,多西他赛在0.2000~3.2000mg/m L浓度范围内,多西他赛峰面积与浓度呈良好的线性关系,R2=0.9998。专属性、日内差日间差以及回收率RSD<5%,均符合要求。药物溶于有机溶剂为O相,2%吐温-20为W相,形成O/W乳液挥发除去有机溶剂得到纳米粒,以包封率、载药量、粒径以及Zeta电位为指标,通过单因素考察进行处方筛选。采用水提醇沉法提取灵芝多糖,葡聚糖凝胶Sephadex G-75柱色谱分离得到灵芝多糖GLP-1。通过Zeta电位测定灵芝多糖GLP-1荷负电,选择十八胺制备正电荷载药纳米粒,使多糖分子由于正负电荷吸引被吸附到纳米粒表面,形成灵芝多糖吸附载药纳米粒。结果:以多西他赛市售制剂为对照,考察纳米粒在高温和光照下的稳定性,结果表明纳米粒药物降解速率低于市售制剂,需避光低温保存。以0.5%吐温-80的p H为7.2的PBS溶液为释放介质进行体外释放,测定药物累计释放百分率,实验表明,纳米粒无突释现象且具有缓释作用,释放率在70%左右。多西他赛纳米粒溶液为注射液,选择人脐静脉内皮细胞Huvec进行安全性评价,MTT细胞毒性结果表明,GLP-PEG-Dox Nps纳米粒溶液对人脐静脉内皮细胞Huvec的安全性较高,PEG-Dox Nps纳米粒溶液对人脐静脉内皮细胞Huvec的安全性居中,多西他赛市售制剂对人脐静脉内皮细胞Huvec的安全性较低。考察纳米粒对人乳腺癌细胞MCF-7的体外抑瘤效果,对MCF-7抑瘤效果较好的是GLP-PEG-Dox NPs纳米粒溶液,其次是PEG-Dox NPs纳米粒溶液,最后是多西他赛市售制剂。动物实验建立小鼠乳腺癌模型评价体内抑瘤效果。多西他赛注射液肿瘤生长抑制率为64.53%,PEG-Dox Nps肿瘤生长抑制率为71.45%;GLP-PEG-Dox Nps肿瘤生长抑制率为78.21%。肿瘤生长抑制率均大于40%,与市售制剂相比P<0.05,有统计学差异。结论:灵芝多糖吸附载药纳米粒处方组成为多西他赛6.0 mg;卵磷脂80.0 mg;十八胺6.0 mg;DSPE-PEG2000 15.0 mg;GLP-1 15.0 mg。纳米粒溶液呈澄清透明乳液,平均粒径为126.4 nm,Zeta电位为-6.25 m V,包封率91.6%,载药量为5.14%。本实验制备的灵芝多糖吸附多西他赛纳米粒与市售制剂相比,具有增强疗效,延长药物时间等优点,为靶向纳米粒制剂的下一步研究奠定基础。
Abstract
mu qian ,you yu sheng huo ya li jia da yi ji huan jing e hua deng yin su ai zheng fa bing lv bu duan shang sheng ,ai zheng yi cheng wei wo guo zhu yao si wang yuan yin zhi yi 。shou shu qie chu 、fang she zhi liao he hua xue zhi liao shi mu qian zhi liao ai zheng de zhu yao shou duan ,dan dou cun zai yi ding de ju xian xing 。wei le gai shan hua liao yao wu de wen ti ,xin xing yao wu di song ji tong de yan jiu shi kang zhong liu yao wu de yan jiu re dian 。na mi yao wu di song ji tong ke cai yong sheng wu jiang jie xing liang hao de cai liao di gao yao wu rong jie du ,di gao ba xiang xing jian shao dui ji ta zu zhi de sun hai 。mu de :duo xi ta sai ,zi sha wan lei ban ge cheng kang zhong liu yao wu ,wei guan dan bai yi zhi ji 。ben wen yi duo xi ta sai wei zhu yao ,yi luan lin zhi wei zai ti cai liao ,shi yong O/Wru hua rong ji hui fa fa zhi bei na mi li ,shi ba an wei zheng dian he diao jie ji ,cai yong DSPE-PEG2000jin hang na mi li xiu shi ,β-ling zhi pu ju tang li yong zheng fu dian he xi fu zuo yong bao fu zai zheng dian he na mi li biao mian ,Zetadian wei ce ding ke zhi ling zhi duo tang xi fu duo xi ta sai na mi li dai fu dian 。dui na mi li de bao feng lv 、zai yao liang 、li jing ji ji Zetadian wei jin hang biao zheng 。yi duo xi ta sai shi shou zhi ji wei dui zhao ,kao cha na mi li de ti wai shi fang he wen ding xing ,ping jia na mi li dui zhong liu xi bao de xi bao du zuo yong he he liu xiao shu de ti nei yi liu xiao guo ,wei na mi li de xia yi bu yan jiu di gong li lun shang de zhi dao 。fang fa :ben shi yan tong guo O/Wru hua rong ji hui fa fa zhi bei le duo xi ta sai na mi li ,jian li le gao xiao ye xiang se pu fa ce ding duo xi ta sai na mi li han liang ce ding fang fa ,liu dong xiang wei yi jing ︰shui =55︰45,liu su wei 1.0m L/min,que ding zi wai jian ce bo chang wei 230 nm。jin hang fang fa xue yan zheng ,duo xi ta sai zai 0.2000~3.2000mg/m Lnong du fan wei nei ,duo xi ta sai feng mian ji yu nong du cheng liang hao de xian xing guan ji ,R2=0.9998。zhuan shu xing 、ri nei cha ri jian cha yi ji hui shou lv RSD<5%,jun fu ge yao qiu 。yao wu rong yu you ji rong ji wei Oxiang ,2%tu wen -20wei Wxiang ,xing cheng O/Wru ye hui fa chu qu you ji rong ji de dao na mi li ,yi bao feng lv 、zai yao liang 、li jing yi ji Zetadian wei wei zhi biao ,tong guo chan yin su kao cha jin hang chu fang shai shua 。cai yong shui di chun chen fa di qu ling zhi duo tang ,pu ju tang ning jiao Sephadex G-75zhu se pu fen li de dao ling zhi duo tang GLP-1。tong guo Zetadian wei ce ding ling zhi duo tang GLP-1he fu dian ,shua ze shi ba an zhi bei zheng dian he zai yao na mi li ,shi duo tang fen zi you yu zheng fu dian he xi yin bei xi fu dao na mi li biao mian ,xing cheng ling zhi duo tang xi fu zai yao na mi li 。jie guo :yi duo xi ta sai shi shou zhi ji wei dui zhao ,kao cha na mi li zai gao wen he guang zhao xia de wen ding xing ,jie guo biao ming na mi li yao wu jiang jie su lv di yu shi shou zhi ji ,xu bi guang di wen bao cun 。yi 0.5%tu wen -80de p Hwei 7.2de PBSrong ye wei shi fang jie zhi jin hang ti wai shi fang ,ce ding yao wu lei ji shi fang bai fen lv ,shi yan biao ming ,na mi li mo tu shi xian xiang ju ju you huan shi zuo yong ,shi fang lv zai 70%zuo you 。duo xi ta sai na mi li rong ye wei zhu she ye ,shua ze ren qi jing mai nei pi xi bao Huvecjin hang an quan xing ping jia ,MTTxi bao du xing jie guo biao ming ,GLP-PEG-Dox Npsna mi li rong ye dui ren qi jing mai nei pi xi bao Huvecde an quan xing jiao gao ,PEG-Dox Npsna mi li rong ye dui ren qi jing mai nei pi xi bao Huvecde an quan xing ju zhong ,duo xi ta sai shi shou zhi ji dui ren qi jing mai nei pi xi bao Huvecde an quan xing jiao di 。kao cha na mi li dui ren ru xian ai xi bao MCF-7de ti wai yi liu xiao guo ,dui MCF-7yi liu xiao guo jiao hao de shi GLP-PEG-Dox NPsna mi li rong ye ,ji ci shi PEG-Dox NPsna mi li rong ye ,zui hou shi duo xi ta sai shi shou zhi ji 。dong wu shi yan jian li xiao shu ru xian ai mo xing ping jia ti nei yi liu xiao guo 。duo xi ta sai zhu she ye zhong liu sheng chang yi zhi lv wei 64.53%,PEG-Dox Npszhong liu sheng chang yi zhi lv wei 71.45%;GLP-PEG-Dox Npszhong liu sheng chang yi zhi lv wei 78.21%。zhong liu sheng chang yi zhi lv jun da yu 40%,yu shi shou zhi ji xiang bi P<0.05,you tong ji xue cha yi 。jie lun :ling zhi duo tang xi fu zai yao na mi li chu fang zu cheng wei duo xi ta sai 6.0 mg;luan lin zhi 80.0 mg;shi ba an 6.0 mg;DSPE-PEG2000 15.0 mg;GLP-1 15.0 mg。na mi li rong ye cheng cheng qing tou ming ru ye ,ping jun li jing wei 126.4 nm,Zetadian wei wei -6.25 m V,bao feng lv 91.6%,zai yao liang wei 5.14%。ben shi yan zhi bei de ling zhi duo tang xi fu duo xi ta sai na mi li yu shi shou zhi ji xiang bi ,ju you zeng jiang liao xiao ,yan chang yao wu shi jian deng you dian ,wei ba xiang na mi li zhi ji de xia yi bu yan jiu dian ding ji chu 。
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论文作者分别是来自济南大学的毛丽燕，发表于刊物济南大学2019-07-23论文，是一篇关于多西他赛论文,纳米粒论文,稳定性论文,体外释放论文,体内抑瘤效果论文,济南大学2019-07-23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，资料来自济南大学2019-07-23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：多西他赛论文; 纳米粒论文; 稳定性论文; 体外释放论文; 体内抑瘤效果论文; 济南大学2019-07-23论文;