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首页> 外文学位 >Amphiphilic scorpion-like macromolecules (AScMs) and amphiphilic-star like macromolecules (ASMs): Efficient carriers for hydrophobic drugs.
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Amphiphilic scorpion-like macromolecules (AScMs) and amphiphilic-star like macromolecules (ASMs): Efficient carriers for hydrophobic drugs.

机译：两亲类蝎状大分子（AScM）和两亲类星形大分子（ASM）：疏水性药物的有效载体。

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摘要

Polymeric micelles based on amphiphilic scorpion-like macromolecules (AScMs) were prepared by organic solvent/water (O/W) emulsion technique, and evaluated as novel drug delivery vehicle for indomethacin (IMC). Two AScMs block copolymers were investigated for IMC incorporation, M12P 5 and M12P2, respectively. For both AScMs studied, a considerable effect of feed drug:polymer ratio and molecular weight of hydrophilic segment of block copolymer on drug loading content and entrapment efficiency were observed. The sizes of IMC-loaded M12P5 and M 12P2 polymeric micelles were 20 nm with narrow size distribution. In vitro release studies showed that compared to IMC alone, IMC release from M12P5 and M12P 5 polymeric micelles showed sustained release character during 24 h of experiment (p0.05). In vitro cytotoxicity studies, confirmed that M12P5 and M12P2 polymeric micelles did not induce any remarkable cytotoxicity against HUVEC cells up to concentration of 1 and 0.5 mM, respectively. Overall, the results of our investigation show that water-insoluble drug (e.g. indomethacin) was successfully incorporated into the M12P5 and M 12P2 polymeric micelles by optimizing incorporation conditions. However, between two AScMs studied, M12P5 has better potential as a novel drug delivery system for different hydrophobic drugs.; To better understand the fate of polymeric micelles (e.g. amphiphilic scorpion-like macromolecules, AScMs) and unimolecular micelles (e.g., amphiphilic star-like macromolecules, ASMs) in HUVECs, their internalization and intracellular trafficking were investigated. Uptake studies in the presence of metabolic inhibitors revealed that AScMs and ASMs micelles were internalized by non-specific receptor mediated endocytosis as well as fluid phase endocytosis. However, spontaneous non-energy driven processes such as membrane fusion or insertion into cellular membrane may also play a role in the polymer uptake. To examine the intracellular fate of AScMs in HUVECs, polymeric micelles (e.g., M 12P5) were labeled with fluorescein isothiocyanate (FITC). TEM and confocal microscopy studies revealed that following uptake, micelles were localized into cytoplasm as well as the nucleus. In summary, our findings suggest that AScM-based micelle are rapidly internalized into HUVECs; following internalization the AScMs micelles are localized into cytoplasm as well as nucleus. Therefore, AScMs are promising candidate for intracytoplasmic delivery of drugs, proteins and/or genes.
机译：通过有机溶剂/水（O / W）乳液技术制备了基于两亲性蝎子状大分子（AScMs）的高分子胶束，并将其作为消炎痛的新型药物载体。研究了两种AScMs嵌段共聚物的IMC掺入，分别为M12P 5和M12P2。对于所研究的两种AScM，均观察到进料药物：聚合物比率和嵌段共聚物亲水链段的分子量对药物负载量和包封效率有相当大的影响。载有IMC的M12P5和M 12P2聚合物胶束的尺寸<20 nm，尺寸分布狭窄。体外释放研究表明，与单独使用IMC相比，从M12P5和M12P 5聚合物胶束释放的IMC在实验的24小时内显示出持续释放的特征（p <0.05）。体外细胞毒性研究证实，分别达到1和0.5 mM的浓度，M12P5和M12P2聚合胶束不会对HUVEC细胞产生任何显着的细胞毒性。总体而言，我们的研究结果表明，通过优化掺入条件，水不溶性药物（例如消炎痛）已成功地掺入M12P5和M 12P2聚合物胶束中。然而，在研究的两个AScM之间，M12P5作为用于不同疏水性药物的新型药物递送系统具有更好的潜力。为了更好地了解HUVEC中聚合胶束（例如两亲的蝎子状大分子，AScM）和单分子胶束（例如两亲的星状大分子，ASM）的命运，对其内在化和细胞内运输进行了研究。在代谢抑制剂存在下的摄取研究表明，AScMs和ASMs胶束被非特异性受体介导的内吞作用以及液相内吞作用所内化。但是，自发的非能量驱动过程（例如膜融合或插入细胞膜）也可能在聚合物吸收中起作用。为了检查HUVEC中AScM的细胞内命运，用异硫氰酸荧光素（FITC）标记聚合物胶束（例如M 12P5）。 TEM和共聚焦显微镜研究表明，摄取后，胶束定位于细胞质以及细胞核中。总而言之，我们的发现表明基于AScM的胶束迅速内化到HUVEC中。内化后，AScMs胶束定位在细胞质和细胞核中。因此，AScMs是药物，蛋白质和/或基因胞浆内递送的有希望的候选者。

著录项

  • 作者

    Djordjevic, Jelena.;

  • 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 Health Sciences Pharmacy.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 221 p.
  • 总页数 221
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药剂学;
  • 关键词

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