Tumor targetability and antitumor effect of docetaxel-loaded hydrophobically modified glycol chitosan nanoparticles
Tumor targetability and antitumor effect of docetaxel-loaded hydrophobically modified glycol chitosan nanoparticles
复制标题
DOI：
10.1016/j.jconrel.2008.02.003
复制
发表时间：
2008-05-22
影响因子：
10.8
通讯作者：
Kim, Yong-Hee
中科院分区：
文献类型：
--
作者：
Hwang, Ho-Young;Kim, In-San;Kim, Yong-Hee
将疏水分子胆酸引入到水溶性乙二醇壳聚糖中，制备了一种新型纳米药物载体--疏水改性乙二醇壳聚糖纳米粒。通过透析法将抗癌药物多西紫杉醇(DTX)轻松负载到HGC纳米粒中，得到的载多西紫杉醇纳米粒(DTX-HGC)在水溶液中自发形成平均直径为350 nm的自组装聚集体。DTX-HGC纳米粒在生理条件(pH 7.4和37℃)和体外缓释药物释放2周内具有良好的分散性和稳定性。此外，DTX-HGC纳米粒子在过量的牛血清白蛋白存在下也是相当稳定的，这表明DTX-HGC纳米粒子在血流中也可能是稳定的。DTX-HGC纳米粒子在水条件下表现出独特的变形能力，尽管其平均直径为350 nm，但它们可以很容易地通过具有200 nm孔径的滤膜。我们还利用非侵入性活体动物成像技术评估了DTX-HGC纳米粒的时间依赖性排泄曲线、体内生物分布、延长循环时间和肿瘤靶向能力。最后，在肿瘤治疗的最佳条件下，DTX-HGC纳米粒与游离DTX相比，在A549肺癌细胞荷瘤小鼠中显示出更高的抗肿瘤效果，如缩小肿瘤体积和提高存活率，并显著降低了抗癌药物的毒性。综上所述，我们的研究结果表明，负载抗癌药物的纳米载体是一种很有前途的抗癌纳米药物制剂。(C)2008爱思唯尔B.V.保留所有权利。
Hydrophobically modified glycol chitosan (HGC) nanoparticles, a new nano-sized drug carrier, were prepared by introducing a hydrophobic molecule, cholanic acid, to water soluble glycol chitosan. The HGC nanoparticles were easily loaded with the anticancer drug docetaxel (DTX) using a dialysis method, and the resulting docetaxel-loaded HGC (DTX-HGC) nanoparticles formed spontaneously self-assembled aggregates with a mean diameter of 350 nm in aqueous condition. The DTX-HGC nanoparticles were well dispersed and stable for 2 weeks under physiological conditions (pH 7.4 and 37 degrees C) and a sustained drug release profile, in vitro. In addition, the DTX-HGC nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the DTX-HGC nanoparticles might also be stable in the blood stream. The DTX-HGC nanoparticles exhibited a distinctive deformability in aqueous conditions, in that they could easily pass through a filter membrane with 200 nm pores despite their mean diameter of 350 nm. We also evaluated the time-dependent excretion profile, in vivo biodistribution, prolonged circulation time, and tumor targeting ability of DTX-HGC nanoparticles by using a non-invasive live animal imaging technology. Finally, under optimal conditions for cancer therapy, the DTX-HGC nanoparticles showed higher antitumor efficacy such as reduced tumor volume and increased survival rate in A549 lung cancer cells-bearing mice and strongly reduced the anticancer drug toxicity compared to that of free DTX in tumor-bearing mice. Together our results showed that the anticancer loaded nano-sized drug carriers are a promising nanosized drug formulation for cancer therapy. (C) 2008 Elsevier B.V. All rights reserved.