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用于胶质母细胞瘤治疗的雷帕霉素从静电纺丝PEO/PDLLA纳米纤维的局部体外递送

Local in vitro delivery of rapamycin from electrospun PEO/PDLLA nanofibers for glioblastoma treatment.

作者信息

Wang Benlin, Li Haoyuan, Yao Qingyu, Zhang Yulin, Zhu Xiaodong, Xia Tongliang, Wang Jian, Li Gang, Li Xingang, Ni Shilei

机构信息

Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan 250012, China.

Affiliated Hospital of Jining Medical University, Jining 272000, China.

出版信息

Biomed Pharmacother. 2016 Oct;83:1345-1352. doi: 10.1016/j.biopha.2016.08.033. Epub 2016 Aug 28.

Abstract

Rapamycin, a mammalian target of rapamycin inhibitor and anti-proliferative agent, is used to treat glioma and other malignancies, but its effectiveness is limited by the fact that it cannot be delivered in a targeted manner to the site of the tumor. To address this issue, we fabricated a mesh via electrospinning using two biodegradable materials, poly(lactic acid) (PLA) and polyethylene oxide (PEO) as a carrier for rapamycin delivery to the tumor. Nanofiber diameter decreased with increasing PLA concentration in the mixed solution. Scanning electron microscopy analysis revealed the smooth and uniform surface morphology of hybrid fibers. Fourier transform infrared spectroscopy analysis demonstrated that rapamycin was encapsulated in the polymer solution; encapsulation efficiency was high and stable over the range of drug concentrations from 0.5-2wt%. A correlation was observed between sustained release of the drug in vitro and cytotoxicity in cultured glioma cells. These results indicate that the PEO/poly(d,l-lactic acid) nanofiber mesh can be used as a targeted delivery system for rapamycin that can limit side effects and prevent locoregional recurrence following surgical resection of glioma.

摘要

雷帕霉素是一种雷帕霉素哺乳动物靶点抑制剂和抗增殖剂,用于治疗神经胶质瘤和其他恶性肿瘤,但其有效性受到无法以靶向方式递送至肿瘤部位这一事实的限制。为了解决这个问题,我们通过静电纺丝使用两种可生物降解材料——聚乳酸(PLA)和聚环氧乙烷(PEO)制备了一种网,作为将雷帕霉素递送至肿瘤的载体。混合溶液中随着PLA浓度的增加,纳米纤维直径减小。扫描电子显微镜分析显示了混合纤维表面光滑且均匀的形态。傅里叶变换红外光谱分析表明雷帕霉素被包裹在聚合物溶液中;在0.5 - 2wt%的药物浓度范围内,包封效率高且稳定。在体外药物的持续释放与培养的神经胶质瘤细胞的细胞毒性之间观察到相关性。这些结果表明,PEO/聚(d,l-乳酸)纳米纤维网可作为雷帕霉素的靶向递送系统,其可以限制副作用并防止神经胶质瘤手术切除后的局部复发。

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