Parichehr Hassanzadeh1, Elham Arbabi2, Fatemeh Atyabi3, Rassoul Dinarvand4. 1. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Neurological Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: p-hassanzadeh@razi.tums.ac.ir. 2. Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: arbabiavalelham@gmail.com. 3. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: atyabifa@tums.ac.ir. 4. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Dinarvand@tums.ac.ir.
Abstract
AIMS: The therapeutic potential of nerve growth factor (NGF) against the neurological disorders may be negatively affected by its short half-life. Based on the superior properties of carbon nanotubes (CNTs) for controlled drug delivery, we aimed to prepare CNT-NGF complex and evaluate its effect in an in vitro model of ischemic stroke. MATERIALS AND METHODS: Multi-walled CNTs (MWCNTs)-NGF complex was prepared using amino-functionalized COOH-MWCNTs and characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. PC12 cells in the absence or presence of NGF (0.5, 1, 2μg/ml), acid- or amine-modified MWCNTs, or MWCNTs-NGF complex (2, 4, 8μg/ml) were exposed to 1 and 6h oxygen-glucose deprivation (OGD) followed by 24h re-oxygenation. Cytotoxicity and oxidative stress were evaluated. KEY FINDINGS: OGD significantly reduced the cell viability (P<0.001). NGF dose-dependently increased the cell viability only after 1-h OGD (P<0.05), while, MWCNTs-NGF complex was effective at both 1- and 6-h OGD (P<0.05, P<0.001). NGF reduced the formation of condensed nuclei due to 1-h OGD (P<0.01, P<0.001), while, MWCNTs-NGF showed efficiency at both time points (P<0.05, P<0.01, P<0.001). OGD significantly increased malondialdehyde (MDA) content and decreased catalase (CAT) and superoxide dismutase (SOD) activities (P<0.001). After 1-h OGD, NGF reduced MDA (P<0.001) and increased CAT (P<0.05, P<0.01) and SOD (P<0.01), while, MWCNTs-NGF was effective after both 1- and 6-h OGD (MDA: P<0.01, P<0.001, CAT: P<0.001, SOD: P<0.01, P<0.001). SIGNIFICANCE: Aminated MWCNTs-NGF complex by providing longer lasting effects for NGF might be of therapeutic significance against the disorders associated with NGF deficiency.
AIMS: The therapeutic potential of nerve growth factor (NGF) against the neurological disorders may be negatively affected by its short half-life. Based on the superior properties of carbon nanotubes (CNTs) for controlled drug delivery, we aimed to prepare CNT-NGF complex and evaluate its effect in an in vitro model of ischemic stroke. MATERIALS AND METHODS: Multi-walled CNTs (MWCNTs)-NGF complex was prepared using amino-functionalized COOH-MWCNTs and characterized by Fourier transform infrared spectroscopy and transmission electron microscopy. PC12 cells in the absence or presence of NGF (0.5, 1, 2μg/ml), acid- or amine-modified MWCNTs, or MWCNTs-NGF complex (2, 4, 8μg/ml) were exposed to 1 and 6h oxygen-glucose deprivation (OGD) followed by 24h re-oxygenation. Cytotoxicity and oxidative stress were evaluated. KEY FINDINGS: OGD significantly reduced the cell viability (P<0.001). NGF dose-dependently increased the cell viability only after 1-h OGD (P<0.05), while, MWCNTs-NGF complex was effective at both 1- and 6-h OGD (P<0.05, P<0.001). NGF reduced the formation of condensed nuclei due to 1-h OGD (P<0.01, P<0.001), while, MWCNTs-NGF showed efficiency at both time points (P<0.05, P<0.01, P<0.001). OGD significantly increased malondialdehyde (MDA) content and decreased catalase (CAT) and superoxide dismutase (SOD) activities (P<0.001). After 1-h OGD, NGF reduced MDA (P<0.001) and increased CAT (P<0.05, P<0.01) and SOD (P<0.01), while, MWCNTs-NGF was effective after both 1- and 6-h OGD (MDA: P<0.01, P<0.001, CAT: P<0.001, SOD: P<0.01, P<0.001). SIGNIFICANCE: Aminated MWCNTs-NGF complex by providing longer lasting effects for NGF might be of therapeutic significance against the disorders associated with NGF deficiency.
Authors: T A Gudasheva; P Yu Povarnina; A A Volkova; S V Kruglov; T A Antipova; S B Seredenin Journal: Acta Naturae Date: 2019 Jul-Sep Impact factor: 1.845