Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase

Elahe Karimi,1,2 Shahryar Abbasi,1,3 Naser Abbasi2,41Department of Chemistry, Ilam Branch, Islamic Azad University, Ilam, Iran; 2Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran; 3Department of Chemistry, Faculty of Science, Ilam U...

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Main Authors: Karimi E, Abbasi S, Abbasi N
Format: Article
Language:English
Published: Dove Medical Press 2019-07-01
Series:Drug Design, Development and Therapy
Subjects:
Online Access:https://www.dovepress.com/thymol-polymeric-nanoparticle-synthesis-and-its-effects-on-the-toxicit-peer-reviewed-article-DDDT
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author Karimi E
Abbasi S
Abbasi N
author_facet Karimi E
Abbasi S
Abbasi N
author_sort Karimi E
collection DOAJ
description Elahe Karimi,1,2 Shahryar Abbasi,1,3 Naser Abbasi2,41Department of Chemistry, Ilam Branch, Islamic Azad University, Ilam, Iran; 2Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran; 3Department of Chemistry, Faculty of Science, Ilam University, Ilam, Iran; 4Department of Pharmacology, Medical School, Ilam University of Medical Sciences, Ilam, IranBackground: 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.Keywords: thymol, polymeric nanoparticle, olfactory enshealing cell, drug delivery, high glucose
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spelling doaj.art-0ebeeb7bd7804f0891006f2f5252a54e2022-12-21T17:56:38ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-07-01Volume 132513253247409Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinaseKarimi EAbbasi SAbbasi NElahe Karimi,1,2 Shahryar Abbasi,1,3 Naser Abbasi2,41Department of Chemistry, Ilam Branch, Islamic Azad University, Ilam, Iran; 2Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran; 3Department of Chemistry, Faculty of Science, Ilam University, Ilam, Iran; 4Department of Pharmacology, Medical School, Ilam University of Medical Sciences, Ilam, IranBackground: 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.Keywords: thymol, polymeric nanoparticle, olfactory enshealing cell, drug delivery, high glucosehttps://www.dovepress.com/thymol-polymeric-nanoparticle-synthesis-and-its-effects-on-the-toxicit-peer-reviewed-article-DDDTThymolnanopolymerolfactory enshealing celldrug deliveryhigh glucose
spellingShingle Karimi E
Abbasi S
Abbasi N
Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase
Drug Design, Development and Therapy
Thymol
nanopolymer
olfactory enshealing cell
drug delivery
high glucose
title Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase
title_full Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase
title_fullStr Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase
title_full_unstemmed Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase
title_short Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase
title_sort thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on oec cells involvement of growth factors and integrin linked kinase
topic Thymol
nanopolymer
olfactory enshealing cell
drug delivery
high glucose
url https://www.dovepress.com/thymol-polymeric-nanoparticle-synthesis-and-its-effects-on-the-toxicit-peer-reviewed-article-DDDT
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