基于硫酸软骨素的还原敏感型纳米粒用于黑色素瘤靶向递药的研究
发布时间:2022-01-25 14:30
目前,恶性肿瘤仍然是严重威胁人类生命和健康的主要疾病。在临床实践中,化学疗法仍是主要治疗方法。然而,大多数化疗药物的疗效受到水溶性低、稳定性差、副作用严重以及对肿瘤组织缺乏选择性的困扰。基于多糖的两亲性聚合物可以在水溶液中自组装形成纳米粒,并且避免有机溶液的使用,这类聚合物在肿瘤靶向药物的递送方面引起了科学家的广泛关注。为了提高化疗疗效,本文开发了一种新型的基于硫酸软骨素的聚合物纳米粒,该纳米粒具有还原敏感性,毒性小,生物相容性好,具有肿瘤靶向性。该项目合成了一种新的聚合物,并用它来制备包载多西他赛(DTX)的纳米粒,该纳米粒可在肿瘤微环境中实现氧化还原响应释药,并通过CD44受体的介导实现黑色素瘤的靶向递药。该研究分为两个部分:(a)以胱胺为连接臂的硫酸软骨素-维生素E琥珀酸酯聚合物(CS-CYS-TOS)的构建以及载模型药物DTX纳米粒的制备。(b)将己二酸二醜肼(ADH)用作连接臂,用于合成非还原敏感型硫酸软骨素-己二酸二酸肼-维生素E琥珀酸酯(CS-ADH-TOS)聚合物,该聚合物可用于构建非还原敏感的纳米系统。纳米粒具有优异的物理和化学性能:小尺寸、窄尺寸分布、高载药量(DL...
【文章来源】:山东大学山东省 211工程院校 985工程院校 教育部直属院校
【文章页数】:126 页
【学位级别】:博士
【部分图文】:
图1-1:?CS-CYS-TOS的合成步骤??1.1?Snthesis?of?CS-CYS??
natant?was?collected?and?lyophilized?to?obtain?final?product?of?CS-ADH-TOS?[72,?75-77].??HjN??Ml.??、、H??or??l?1?+?[DC-、??卜丄??cs?、?'?c,?-^?j??CS-ADH??T〇S?V,?>??EDC,?NHS?"?U\?>??CS-ADH-TOS??Fig.?1-2:?Synthesis?steps?of?CS-ADH-TOS??图1-2:?CS-ADH-TOS的合成步骤??3.?Characterization?of?polymers??3.1?^-NMR?spectrum??Accurately?weighed?(5mg)?CS,?CS-CYS-TOS,?CS-ADH-TOS?and?TOS?were?dissolved?in??35??
S2?1.9??^?CS-CYS-TOS?1?L8.??O?CS-CYS-TOS3??-3?-2.5?-2?-1.5?-1?-0.5?0??log?C?(mg/mL)??Fig.?2-1:?Plot?of?intensity?ratios?(I373/I383)?obtained?from?excitation?spectra?of?pyrene?V.S.?the??logarithmic?concentration?of?CS-CYS-TOS?polymers??图2-1:芘荧光发射光谱I373/Iw荧光强度比值与CS-CYS-TOS聚合物浓度对数值的关??系图??Table?2-1:?The?physiochemical?properties?of?blank?nanoparticles??表2-1:空白纳米粒的理化性质??Polymer?CAC?DS?Size?士?SD?Zeta?Potential?士SD??(mg/mL)?(nm)?(mV)??CS-CYS-TOS?1?0027?4^6?16^1?±?3.7?-16.5?±0.89??CS-CYS-TOS?2?0.031?3.18?187?土?6.2?-14.4?±1.7??CS-CYS-TOS?3?0.040?2.50?220?士?4.5?-11.2士?5.4??CS-ADH-TOS?0.050?5.75?208?±?8.6?-10.4?±7.8??1.2?Investigation?of?particle?size?and?zeta?potential??The?measurement?results?of?si
【参考文献】:
期刊论文
[1]载香豆素6的PEG-PCL胶束跨MDCK极性上皮细胞的转运过程[J]. 于超,何冰,张华,代文兵,王学清,张强. 药学学报. 2013(09)
本文编号:3608703
【文章来源】:山东大学山东省 211工程院校 985工程院校 教育部直属院校
【文章页数】:126 页
【学位级别】:博士
【部分图文】:
图1-1:?CS-CYS-TOS的合成步骤??1.1?Snthesis?of?CS-CYS??
natant?was?collected?and?lyophilized?to?obtain?final?product?of?CS-ADH-TOS?[72,?75-77].??HjN??Ml.??、、H??or??l?1?+?[DC-、??卜丄??cs?、?'?c,?-^?j??CS-ADH??T〇S?V,?>??EDC,?NHS?"?U\?>??CS-ADH-TOS??Fig.?1-2:?Synthesis?steps?of?CS-ADH-TOS??图1-2:?CS-ADH-TOS的合成步骤??3.?Characterization?of?polymers??3.1?^-NMR?spectrum??Accurately?weighed?(5mg)?CS,?CS-CYS-TOS,?CS-ADH-TOS?and?TOS?were?dissolved?in??35??
S2?1.9??^?CS-CYS-TOS?1?L8.??O?CS-CYS-TOS3??-3?-2.5?-2?-1.5?-1?-0.5?0??log?C?(mg/mL)??Fig.?2-1:?Plot?of?intensity?ratios?(I373/I383)?obtained?from?excitation?spectra?of?pyrene?V.S.?the??logarithmic?concentration?of?CS-CYS-TOS?polymers??图2-1:芘荧光发射光谱I373/Iw荧光强度比值与CS-CYS-TOS聚合物浓度对数值的关??系图??Table?2-1:?The?physiochemical?properties?of?blank?nanoparticles??表2-1:空白纳米粒的理化性质??Polymer?CAC?DS?Size?士?SD?Zeta?Potential?士SD??(mg/mL)?(nm)?(mV)??CS-CYS-TOS?1?0027?4^6?16^1?±?3.7?-16.5?±0.89??CS-CYS-TOS?2?0.031?3.18?187?土?6.2?-14.4?±1.7??CS-CYS-TOS?3?0.040?2.50?220?士?4.5?-11.2士?5.4??CS-ADH-TOS?0.050?5.75?208?±?8.6?-10.4?±7.8??1.2?Investigation?of?particle?size?and?zeta?potential??The?measurement?results?of?si
【参考文献】:
期刊论文
[1]载香豆素6的PEG-PCL胶束跨MDCK极性上皮细胞的转运过程[J]. 于超,何冰,张华,代文兵,王学清,张强. 药学学报. 2013(09)
本文编号:3608703
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