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一种纳米聚合物的新型绿色合成及其在正常和高糖条件下大鼠嗅鞘细胞中作为水飞蓟宾和水飞蓟素提取物药物递送系统的应用。

Novel and green synthesis of a nanopolymer and its use as a drug delivery system of silibinin and silymarin extracts in the olfactory ensheathing cells of rats in normal and high-glucose conditions.

作者信息

Shiri Sabah, Abbasi Naser, Alizadeh Kamal, Karimi Elahe

机构信息

Department of Chemistry, Lorestan University Khorramabad 6813717133 Iran

Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences Ilam Iran

出版信息

RSC Adv. 2019 Nov 27;9(67):38912-38927. doi: 10.1039/c9ra05608d.

Abstract

Drug delivery systems have been of interest to researchers. The effects of synthesized nano-polymers as silibinin and silymarin extract drug delivery systems on olfactory ensheathing cells under normal and high-glucose conditions were studied. The structure of the nanopolymer was characterized by IR, HNMR, GPC, DLS, and AFM. The toxicity was evaluated by an MTT assay. The production of ROS and the generation of NO were evaluated by a probe of fluorescein diacetate and Griess methods, respectively. The expressions of the protein levels of ILK, VEGF, BDNF, and NGF were investigated by western blotting. The polymer size was between 50 and 150 nm. The loading capacities for silibinin and silymarin were 68.5% and 56.4%, respectively, and the drug release for them was estimated at 54.1% and 50.8%, respectively. In high-glucose conditions, the cells were protected (EC = 4.88 ± 0.5 μM) by silibinin and nanopolymer in low concentrations by reducing the amount of ROS and NO, maintaining ILK, reducing VEGF and increasing NGF and BDNF. Incubation with silibinin and nanopolymer at high concentrations increased cell death with LC = 57.36 ± 2.5 and 43.18 ± 1.8 μM, respectively, in high-glucose states. Thus, the cells were protected by silibinin and nanopolymer in protective concentrations by reducing the amount of ROS and NO, maintaining ILK, reducing VEGF, and increasing BDNF and NGF. The mentioned mechanisms were totally reversed at high concentrations.

摘要

药物递送系统一直是研究人员感兴趣的领域。研究了合成的纳米聚合物作为水飞蓟宾和水飞蓟素提取物药物递送系统在正常和高糖条件下对嗅鞘细胞的影响。通过红外光谱(IR)、核磁共振氢谱(HNMR)、凝胶渗透色谱(GPC)、动态光散射(DLS)和原子力显微镜(AFM)对纳米聚合物的结构进行了表征。通过MTT法评估毒性。分别通过荧光素二乙酸酯探针和格里斯方法评估活性氧(ROS)的产生和一氧化氮(NO)的生成。通过蛋白质免疫印迹法研究了整合素连接激酶(ILK)、血管内皮生长因子(VEGF)、脑源性神经营养因子(BDNF)和神经生长因子(NGF)蛋白水平的表达。聚合物尺寸在50至150纳米之间。水飞蓟宾和水飞蓟素的载药量分别为68.5%和56.4%,它们的药物释放率估计分别为54.1%和50.8%。在高糖条件下,低浓度的水飞蓟宾和纳米聚合物通过减少ROS和NO的量、维持ILK、降低VEGF以及增加NGF和BDNF来保护细胞(半数有效浓度EC = 4.88 ± 0.5 μM)。在高糖状态下,高浓度的水飞蓟宾和纳米聚合物孵育分别使细胞死亡率增加,半数致死浓度LC = 57.36 ± 2.5 μM和43.18 ± 1.8 μM。因此,在保护浓度下,水飞蓟宾和纳米聚合物通过减少ROS和NO的量、维持ILK、降低VEGF以及增加BDNF和NGF来保护细胞。上述机制在高浓度时完全逆转。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd7/9075964/8d68dbd758e8/c9ra05608d-f1.jpg

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