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Carbon Nanotube-Anandamide Complex Exhibits Sustained Protective Effects in an in Vitro Model of Stroke



Hassanzadeh P1, 2 ; Arbabi E3 ; Atyabi F1, 4 ; Dinarvand R1, 4
Authors
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Authors Affiliations
  1. 1. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Neurological Research Center, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Teheran, Iran

Source: Physiology and Pharmacology Published:2016

Abstract

Introduction: The therapeutic potential of anandamide (AEA) for the neurological disorders may be negatively affected by its short half-life or poor solubility. The superior properties of carbon nanotubes (CNTs) for controlled drug delivery, prompted us to design AEA-CNTs complex and assess its effect in in vitro model of ischemic stroke. Methods: In this experimental study, a multi-walled CNTs (MWCNTs)-AEA complex was prepared using amino-functionalized COOH-MWCNTs and characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. PC12 cells in the presence of AEA (0.5, 1, 2 μg/ml), acid- or amine-modified MWCNTs, or MWCNTs-AEA complex (2, 5, 8 μg/ml) were exposed to 1 and 3 h oxygen-glucose deprivation (OGD) followed by 24 h re-oxygenation. In vitro cytotoxicity and oxidative stress were evaluated using three-way ANOVA. Results: AEA immobilization on the aminated MWCNTs was confirmed. OGD significantly reduced cell viability (P<0.001). After 3 h of OGD induction, COOH-MWCNTs showed higher cytotoxicity than other MWCNTs (P<0.05, P<0.01, P<0.001) and MWCNTs-AEA was more protective than AEA alone (P<0.05, P<0.01). OGD increased malondialdehyde (MDA) and decreased glutathione (GSH) and superoxide dismutase (SOD) (P<0.001). Following 1-h OGD, AEA dose-dependently reduced MDA (P<0.001), and elevated GSH (P<0.05, P<0.01) and SOD (P<0.05, P<0.01), but AEA was ineffective following 3-h OGD (P>0.05). MWCNTs-AEA complex was effective at both time points (MDA and GSH: P<0.01, P<0.001, SOD: P<0.05, P<0.01, P<0.001). This nanostructure was more effective than AEA following longer exposure periods to OGD insult (P<0.05, P<0.01, P<0.001). Conclusion: Aminated MWCNTs are suitable carriers for AEA and provide longer-lasting effects against OGD insult. © 2017, Iranian Society of Physiology and Pharmacology. All rights reserved.
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