• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Preparation and evaluation of amphiphilic macromolecules-based conjugates and micelles for anticancer drug delivery.
【24h】

Preparation and evaluation of amphiphilic macromolecules-based conjugates and micelles for anticancer drug delivery.

机译：基于两亲大分子的偶联物和胶束的制备和评价，用于抗癌药物的递送。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Micelles assembled from amphiphilic macromolecules (AM) or drug-conjugated AMs were evaluated as anticancer drug carriers in terms of drug content, sustained/controlled drug release and cytotoxicity of encapsulated/bound drug. Physical drug encapsulation was compared with chemical drug conjugation. The AM micelles were compared with known polymeric delivery systems, Pluronic P85 and Cremophor EL. Generally, AM micelles encapsulated drugs as efficiently (or better) than the established polymeric carriers.;Encapsulated hydrophobic drugs in AM micelles showed non-aggregation of drug and sustained drug release after lyophilization and resolubilization in aqueous solutions; indicating good solution and storage stability of drug-loaded AM micelles. Compared to the polymeric controls, the AM micelles showed faster resolubilization times and better pH/temperature micellar stability.;Cellular entry of AM micelles in human umbilical vein endothelial cells was observed to be endocytotic, observed from the colocalization of fluorescein-labeled AMs and fluorescent dye-stained endosomes or lysosomes that were detected by confocal scanning microscopy.;Doxorubicin (DOX) was conjugated to AMs via acidic pH-sensitive hydrazone linkers and the DOX-AM micelles had ∼ 30 nm sizes. DOX-AMs showed higher drug release at lysosomal pH 5.0 as compared to physiological pH 7.4. Cell proliferation assays of DOX-AM micelles showed better cytotoxicity compared to DOX-loaded AM micelles and free DOX against human hepatocellular carcinoma cells.;As another example of drug conjugation, camptothecin (CPT) was conjugated to AMs via glycine linkers. CPT-AM micelles showed CPT lactone stabilization, higher CPT solubilization, and increased stability against human serum albumin (HSA) on CPT release in vitro. However, cell proliferation assays on the CPT-AM micelles showed comparable cytotoxicity to CPT-loaded AM micelles against human colorectal carcinoma cells.;The placement of CPT conjugation was evaluated by CPT conjugation via mucic acid and functionalized alkyl chains. Carbodiimides were used to conjugate CPT to AM mucic acid, whereas click chemistry conjugated alkyne-terminated CPT to azide-terminated AM chains. Higher CPT conjugation was achieved via the functionalized chain ends (i.e. click chemistry) compared to the mucic acid (carbodiimide coupling). However, lesser HSA impact on CPT in vitro release was observed in CPT attached to the mucic acid. Overall, the AM-based micelles showed good characteristics as anticancer drug carriers.
机译：由两亲性大分子（AM）或药物结合的AM组装而成的胶束在药物含量，持续/控制药物释放和包封/结合药物的细胞毒性方面被评估为抗癌药物载体。将物理药物封装与化学药物结合进行了比较。将AM胶束与已知的聚合物输送系统Pluronic P85和Cremophor EL进行比较。通常，AM胶束能比已建立的聚合物载体更有效（或更好）地包裹药物。AM胶束中包裹的疏水性药物在水溶液中冻干和再溶解后显示出药物的非聚集性和持续释放。表明载药AM胶束具有良好的溶液和储存稳定性。与聚合物对照组相比，AM胶束具有更快的再溶解时间和更好的pH /温度胶束稳定性。;通过荧光素标记的AMs和荧光素的共定位，观察到AM胶束进入人脐静脉内皮细胞的细胞具有内吞性通过共聚焦扫描显微镜检测到的染料染色的内体或溶酶体;阿霉素（DOX）通过酸性pH敏感的连接子与AM偶联，DOX-AM胶束的尺寸约为30 nm。与生理pH 7.4相比，DOX-AM在溶酶体pH 5.0时显示出更高的药物释放。与载有DOX的AM胶束和游离的DOX相比，DOX-AM胶束的细胞增殖试验显示出更好的细胞毒性。作为药物偶联的另一个例子，喜树碱（CPT）通过甘氨酸接头与AMs偶联。 CPT-AM胶束在体外释放CPT时显示CPT内酯稳定，较高的CPT增溶性和对人血清白蛋白（HSA）的稳定性。然而，在CPT-AM胶束上进行的细胞增殖试验显示，与载有CPT的AM胶束相比，其对人结肠直肠癌细胞的细胞毒性具有可比性。CPT缀合的位置通过粘蛋白酸和功能化烷基链通过CPT缀合进行评估。碳二亚胺用于将CPT与AM粘酸偶联，而单击化学将炔基封端的CPT与叠氮化物封端的AM链偶联。与粘酸（碳二亚胺偶联）相比，通过官能化的链端（即点击化学）实现了更高的CPT偶联。然而，在粘液上附着的CPT中观察到HSA对CPT体外释放的影响较小。总体而言，基于AM的胶束具有良好的抗癌药物载体特性。

著录项

  • 作者

    Del Rosario, Leilani Singson.;

  • 作者单位

    Rutgers The State University of New Jersey - New Brunswick.;

  • 授予单位 Rutgers The State University of New Jersey - New Brunswick.;
  • 学科 Chemistry Biochemistry.;Chemistry Pharmaceutical.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 165 p.
  • 总页数 165
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号