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首页> 外文期刊>Drug Design, Development and Therapy >Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase
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Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase

机译：百里酚聚合物纳米颗粒的合成及其对高糖对OEC细胞毒性的影响：生长因子和整合素相关激酶的参与

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Background: Nowadays, the drug delivery system is important in the treatment of diseases. Purpose: A polymeric nanoparticle modified by oleic acid (NPMO) as a Thymol (Thy) drug release system was synthesized from Thymbra spicata and its neurotrophic and angiogenic effects on rat’s olfactory ensheathing cells (OECs) in normal (NG) and high glucose (HG) conditions were studied. Methods: The NPMO was characterized by using different spectroscopy methods, such as infrared, HNMR, CNMR, gel permeation chromatography, dynamic light scattering, and atomic force microscopy. Load and releasing were investigated by HPLC. The toxicity against OECs diet-induced by MTT assay. ROS and generation of nitric oxide (NO) were evaluated using dichloro-dihydro-fluorescein and Griess method, respectively. The expression of protein integrin-linked kinase (ILK), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were evaluated by Western blotting. Results: ThyNPMO is desirable for transferring drug as a carrier. The amount of Thy and extract (E) loaded on NPMO estimated at 43±2.5% and 41±1.8%, respectively. Then, 65% and 63% of the drug load were released, respectively. Thy, ThyNPMO, E, and ENPMO prevented HG-induced OECs cell death (EC50 33±1.5, 22±0.9, 35±1.8, and 25±1.1 μM, respectively). Incubation with Thy, ThyNPMO, E ,and ENPMO at high concentrations increased cell death with LC50 105±3.5, 82±2.8, 109±4.3, and 86±3.4 μM, respectively in HG states. Conclusion: OECs were protected by ThyNPMO and ENPMO 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.
机译：背景：如今，药物输送系统在疾病治疗中很重要。目的：从百里香（Thymbra spicata）合成油酸（NPMO）修饰的百里香酚（Thy）药物释放系统的聚合物纳米粒子，其在正常（NG）和高葡萄糖（HG）中对大鼠嗅鞘细胞（OEC）具有神经营养和血管生成作用）条件进行了研究。方法：采用不同的光谱学方法对NPMO进行表征，例如红外光谱，HNMR，CNMR，凝胶渗透色谱，动态光散射和原子力显微镜。通过HPLC研究负荷和释放。 MTT分析对饮食诱导的OEC的毒性。分别使用二氯-二氢荧光素和Griess方法评估ROS和一氧化氮（NO）的生成。通过蛋白质印迹法评估蛋白质整联蛋白连接激酶（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）的表达。结果：ThyNPMO是理想的药物转移载体。装在NPMO上的Thy和提取物（E）的量分别估计为43±2.5％和41±1.8％。然后，分别释放了65％和63％的载药量。 Thy，ThyNPMO，E和ENPMO可防止HG诱导的OEC细胞死亡（分别为EC50 33±1.5、22±0.9、35±1.8和25±1.1μM）。在HG状态下，高浓度Thy，ThyNPMO，E和ENPMO孵育可增加细胞死亡，LC50为105±3.5、82±2.8、109±4.3和86±3.4μM。结论：ThyNPMO和ENPMO可通过减少ROS和NO的含量，维持ILK，降低VEGF以及增加BDNF和NGF的浓度来保护OEC。提到的机制在高浓度下完全相反。

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