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开发一种新型超顺磁纳米载体用于脑胶质瘤的药物递送。

Develop a novel superparamagnetic nano-carrier for drug delivery to brain glioma.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, P.R. China.

出版信息

Drug Deliv. 2013 Apr-May;20(3-4):95-101. doi: 10.3109/10717544.2013.779328. Epub 2013 May 23.

DOI:10.3109/10717544.2013.779328
PMID:23701032
Abstract

Magnetic drug carrier has been employed in drug delivery for over 30 years. Modern nanotechnology has improved its efficiency dramatically by decreasing its diameter into nano-scale. It may help chemotherapeutic agents penetrate BBB and raise local drug concentration in brain, which is the ideal model for glioma treatment. In our study, magnetic carrier was fabricated with octadecyl quaternized caroxymethyl chitosan (OQCMC), hydrophobic Fe₃O₄ ferrofluid and cholesterol, which showed a uniform diameter of 20 nm under transmission electronic microscopy and superparamagnetic character in vibration sample magnetical measurement system. To investigate the efficacy of drug delivery, paclitaxel was used as loaded drug and analyzed by the HPLC. Results showed that magnetic carrier released drugs for more than 20 d in vitro and maintain the drug concentration above 0.4 μg/g for 16 h in rat brain after magnetic targeting. Drug concentration increased by 1-3 folds when delivered by carrier without magnetic targeting, and by 3-15 folds after magnetic targeting. Cellular study revealed that the magnetic carrier was clearly localized in the targeted cortex neural cells and U251-MG cell lines. These results showed that this magnetic carrier is capable of maintaining high drug concentration in magnetically targeted area and carrying drugs or genes into cells, which is potentially promising for local chemotherapy to brain tumors.

摘要

磁性药物载体在药物输送中已经使用了 30 多年。现代纳米技术通过将其直径减小到纳米级,极大地提高了其效率。它可以帮助化疗药物穿透血脑屏障并提高脑内局部药物浓度,这是治疗脑肿瘤的理想模型。在我们的研究中,磁性载体是由十八烷基季铵化羧甲基壳聚糖(OQCMC)、疏水性 Fe3O4 铁磁流体和胆固醇制成的,在透射电子显微镜下显示出均匀的 20nm 直径,在振动样品磁强计中表现出超顺磁性。为了研究药物输送的效果,我们使用紫杉醇作为负载药物,并通过 HPLC 进行分析。结果表明,磁性载体在体外释放药物超过 20d,并在磁靶向后 16h 内使大鼠脑组织中的药物浓度保持在 0.4μg/g 以上。无磁靶向时,载体输送的药物浓度增加了 1-3 倍,磁靶向后增加了 3-15 倍。细胞研究表明,磁性载体明显定位于靶向皮质神经细胞和 U251-MG 细胞系。这些结果表明,这种磁性载体能够在磁靶向区域维持高药物浓度,并将药物或基因输送到细胞中,这对于脑肿瘤的局部化疗具有很大的潜力。

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