The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs
The intracellular effects of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs
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DOI：
10.1016/j.biomaterials.2008.09.035
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发表时间：
2009-01-01
期刊：
影响因子：
14
通讯作者：
Sciortino, Maria T.
中科院分区：
文献类型：
--
作者：
Quaglia, Fabiana;Ostacolo, Luisanna;Sciortino, Maria T.
本研究的目的是开发由两亲性环糊精七（2-O-寡（环氧乙烷）-6-十六烷基硫代-）-β-CD（SC 160 H）制成的包封多西他赛（Doc）的纳米粒，并建立其体内潜力。采用乳化-溶剂挥发法制备了载药SC 160 H纳米粒，并对其粒径、Zeta电位、载药量、释放速率和降解速率进行了表征。球形囊泡纳米颗粒显示出约95 nm的流体动力学半径，其在作为水性分散体储存时不改变，产生了负ζ电位和非常接近100%的Doc包封率。DSC研究强调了SC 160 H、未负载和负载Doc的SC 160 H纳米颗粒的结晶性质，这导致它们在释放阶段非常缓慢的溶解和包埋Doc的良好调节释放约8周。与显示剂量依赖性毒性的市售Doc制剂（Taxotere（R））相比，装载Doc的SC 160 H纳米颗粒对红细胞不具有溶血性。在将HEp-2细胞暴露于等效剂量的游离Doc和Doc负载的SC 160 H纳米颗粒后，观察到纳米颗粒的上级细胞杀伤和细胞损伤。最后，细胞损伤归因于异常的有丝分裂，发现与游离Doc相比，用Doc-负载的SC 160 H纳米颗粒处理的HEp-2细胞的有丝分裂显著更高，这可能是由于纳米颗粒缓慢释放药物的能力，从而允许有丝分裂中延长的细胞停滞。总之，这些结果突出了基于SC 160 H的纳米颗粒在实体肿瘤治疗中的巨大潜力。(C)2008爱思唯尔有限公司保留所有权利。
The aim of this study was to develop nanoparticles made of the amphiphilic cyclodextrin heptakis (2-O-oligo(ethyleneoxide)-6-hexadecylthio-)-beta-CD (SC160H) entrapping docetaxel (Doc) and establish their in vivo potential. Doc-loaded SC160H nanoparticles were prepared by the emulsion-solvent evaporation technique and fully characterized for size, zeta potential, amount of entrapped drug, release rate and degradation rate. Spherical vesicular nanoparticles displaying a hydrodynamic radius of about 95 nm which did not change upon storage as an aqueous dispersion, a negative zeta potential and entrapment efficiency of Doc very close to 100% were produced. DSC study highlighted the crystalline nature of SC160H, unloaded and Doc-loaded SC160H nanoparticles which resulted in their very slow dissolution during release stage and well-modulated release of entrapped Doc for about 8 weeks. Doc-loaded SC160H nanoparticles were not hemolytic toward red blood cells as compared to a commercial Doc formulation (Taxotere (R)) which shows a dose-dependent toxicity. After exposure of HEp-2 cells to equivalent doses of free Doc and Doc-loaded SC160H nanoparticles, superior cell killing and cell damage were observed for nanoparticles. Finally, cell damage was attributed to aberrant mitosis which was found to be significantly higher for HEp-2 cells treated with Doc-loaded SC160H nanoparticles as compared to free Doc likely due to the ability of nanoparticles to slowly release the drug allowing prolonged cell arrest in mitosis. Taken together, these results highlights a great potential of nanoparticles based on SC160H in solid tumors therapy. (C) 2008 Elsevier Ltd. All rights reserved.