Brain-Targeted Delivery of Docetaxel by Glutathione-Coated Nanoparticles for Brain Cancer
Brain-Targeted Delivery of Docetaxel by Glutathione-Coated Nanoparticles for Brain Cancer
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DOI：
10.1208/s12249-014-0165-0
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发表时间：
2014-12-01
影响因子：
3.3
通讯作者：
Sutariya, Vijaykumar
中科院分区：
文献类型：
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作者：
Grover, Aditya;Hirani, Anjali;Sutariya, Vijaykumar
神经胶质瘤是一些最具侵袭性的癌症类型，但血脑屏障是脑相关疾病治疗干预的障碍。血脑屏障通过脑内皮细胞与神经胶质细胞（星形胶质细胞和周细胞）的相互作用阻断潜在毒性化合物渗透到神经组织中，所述神经胶质细胞诱导毛细血管内衬的内皮细胞中紧密连接的形成。在本研究中，我们表征谷胱甘肽涂层紫杉醇负载PEG-PLGA纳米粒，显示其体外药物释放数据沿着与C6和RG 2细胞的细胞毒性数据，并通过建立Transwell细胞共培养研究其跨血脑屏障渗透。我们表明，紫杉醇负载的纳米颗粒的大小，使其trans-blood-brain barrier渗透;纳米颗粒表现出稳定，持续释放多西他赛;药物能够诱导胶质瘤模型中的细胞死亡;和谷胱甘肽涂层的纳米颗粒能够渗透通过Transwell在体外血脑屏障模型。
Gliomas are some of the most aggressive types of cancers but the blood-brain barrier acts as an obstacle to therapeutic intervention in brain-related diseases. The blood-brain barrier blocks the permeation of potentially toxic compounds into neural tissue through the interactions of brain endothelial cells with glial cells (astrocytes and pericytes) which induce the formation of tight junctions in endothelial cells lining the blood capillaries. In the present study, we characterize a glutathione-coated docetaxel-loaded PEG-PLGA nanoparticle, show its in vitro drug release data along with cytotoxicity data in C6 and RG2 cells, and investigate its trans-blood-brain barrier permeation through the establishment of a Transwell cellular co-culture. We show that the docetaxel-loaded nanoparticle's size enables its trans-blood-brain barrier permeation; the nanoparticle exhibits a steady, sustained release of docetaxel; the drug is able to induce cell death in glioma models; and the glutathione-coated nanoparticle is able to permeate through the Transwell in vitro blood-brain barrier model.