Prophylactic and Therapeutic Effects of MOG-Conjugated PLGA Nanoparticles in C57Bl/6 Mouse Model of Multiple Sclerosis

Purpose: Multiple sclerosis (MS) is a debilitating neuroinflammatory disorder of the central nervous system. It is believed to result from an impaired immune response against myelin components especially myelin oligodendrocyte glycoprotein (MOG). Some efforts have been made to bioconjugate the MOG p...

Full description

Bibliographic Details
Main Authors: Mehrdad Gholamzad, Hussein Baharlooi, Mehdi Shafiee Ardestani, Zeinab Seyedkhan, Maryam Azimi
Format: Article
Language:English
Published: Tabriz University of Medical Sciences 2021-06-01
Series:Advanced Pharmaceutical Bulletin
Subjects:
Online Access:https://apb.tbzmed.ac.ir/PDF/apb-11-505.pdf
_version_ 1819349650734317568
author Mehrdad Gholamzad
Hussein Baharlooi
Mehdi Shafiee Ardestani
Zeinab Seyedkhan
Maryam Azimi
author_facet Mehrdad Gholamzad
Hussein Baharlooi
Mehdi Shafiee Ardestani
Zeinab Seyedkhan
Maryam Azimi
author_sort Mehrdad Gholamzad
collection DOAJ
description Purpose: Multiple sclerosis (MS) is a debilitating neuroinflammatory disorder of the central nervous system. It is believed to result from an impaired immune response against myelin components especially myelin oligodendrocyte glycoprotein (MOG). Some efforts have been made to bioconjugate the MOG peptides to tolerogenic particles like poly (lactic-co-glycolic acid) (PLGA) for treating animal models of autoimmune disorders. Accordingly, we aimed to elucidate the tolerogenic effects of MOG-PLGA particles on experimental autoimmune encephalomyelitis (EAE). Methods: PGLA nanoparticles were synthesized using water/oil/water procedure. Next, the MOG or ovalbumin (OVA) peptides covalently linked to the PLGA particles. These particles were then intravenously or subcutaneously administered to nine groups of C57BL/6 mice before and after EAE induction. The brain tissues were assessed for the infiltration of immune cells. The Tolerogenic effect of the vaccine was also assessed on the quantity of the Treg cells. Moreover, the amount of interferon-γ (IFN-γ), interleukin-10 (IL-10), and interleukin-17 levels produced by splenic lymphocytes were then quantified by ELISA. Results: Intravenous administration of PLGA500-MOG35-55 nanoparticles before EAE induction ameliorated EAE clinical scores as well as infiltration of immune cells into the brain. In the spleen, the treatment increased CD4+CD25+FoxP3+ Treg population and restored the homeostasis of IFN-γ, IL-10, and IL-17 (all P values <0.0001) among splenocytes. Conclusion: The conjugation of MOG peptides to the PLGA nanoparticles significantly recovered clinical symptoms and the autoimmune response of EAE. The MOG-PGLA particles are potentially valuable for further evaluations, hopefully progressing toward an optimal approach that can be translated to the clinic.
first_indexed 2024-12-24T19:03:54Z
format Article
id doaj.art-06ce98cfba274e44a5e716c56d4101b3
institution Directory Open Access Journal
issn 2228-5881
2251-7308
language English
last_indexed 2024-12-24T19:03:54Z
publishDate 2021-06-01
publisher Tabriz University of Medical Sciences
record_format Article
series Advanced Pharmaceutical Bulletin
spelling doaj.art-06ce98cfba274e44a5e716c56d4101b32022-12-21T16:43:08ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082021-06-0111350551310.34172/apb.2021.058apb-28519Prophylactic and Therapeutic Effects of MOG-Conjugated PLGA Nanoparticles in C57Bl/6 Mouse Model of Multiple SclerosisMehrdad Gholamzad0Hussein Baharlooi1Mehdi Shafiee Ardestani2Zeinab Seyedkhan3Maryam Azimi4Department of Microbiology and Immunology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.Department of Biology, College of Basic Science, Tehran Science and Research Branch, Islamic Azad University, Tehran, Iran.Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.Purpose: Multiple sclerosis (MS) is a debilitating neuroinflammatory disorder of the central nervous system. It is believed to result from an impaired immune response against myelin components especially myelin oligodendrocyte glycoprotein (MOG). Some efforts have been made to bioconjugate the MOG peptides to tolerogenic particles like poly (lactic-co-glycolic acid) (PLGA) for treating animal models of autoimmune disorders. Accordingly, we aimed to elucidate the tolerogenic effects of MOG-PLGA particles on experimental autoimmune encephalomyelitis (EAE). Methods: PGLA nanoparticles were synthesized using water/oil/water procedure. Next, the MOG or ovalbumin (OVA) peptides covalently linked to the PLGA particles. These particles were then intravenously or subcutaneously administered to nine groups of C57BL/6 mice before and after EAE induction. The brain tissues were assessed for the infiltration of immune cells. The Tolerogenic effect of the vaccine was also assessed on the quantity of the Treg cells. Moreover, the amount of interferon-γ (IFN-γ), interleukin-10 (IL-10), and interleukin-17 levels produced by splenic lymphocytes were then quantified by ELISA. Results: Intravenous administration of PLGA500-MOG35-55 nanoparticles before EAE induction ameliorated EAE clinical scores as well as infiltration of immune cells into the brain. In the spleen, the treatment increased CD4+CD25+FoxP3+ Treg population and restored the homeostasis of IFN-γ, IL-10, and IL-17 (all P values <0.0001) among splenocytes. Conclusion: The conjugation of MOG peptides to the PLGA nanoparticles significantly recovered clinical symptoms and the autoimmune response of EAE. The MOG-PGLA particles are potentially valuable for further evaluations, hopefully progressing toward an optimal approach that can be translated to the clinic.https://apb.tbzmed.ac.ir/PDF/apb-11-505.pdfmultiple sclerosisexperimental autoimmune encephalomyelitismyelin oligodendrocyte glycoproteinpoly (lactic-co-glycolic acid)regulatory t cellimmune tolerancebiomaterials
spellingShingle Mehrdad Gholamzad
Hussein Baharlooi
Mehdi Shafiee Ardestani
Zeinab Seyedkhan
Maryam Azimi
Prophylactic and Therapeutic Effects of MOG-Conjugated PLGA Nanoparticles in C57Bl/6 Mouse Model of Multiple Sclerosis
Advanced Pharmaceutical Bulletin
multiple sclerosis
experimental autoimmune encephalomyelitis
myelin oligodendrocyte glycoprotein
poly (lactic-co-glycolic acid)
regulatory t cell
immune tolerance
biomaterials
title Prophylactic and Therapeutic Effects of MOG-Conjugated PLGA Nanoparticles in C57Bl/6 Mouse Model of Multiple Sclerosis
title_full Prophylactic and Therapeutic Effects of MOG-Conjugated PLGA Nanoparticles in C57Bl/6 Mouse Model of Multiple Sclerosis
title_fullStr Prophylactic and Therapeutic Effects of MOG-Conjugated PLGA Nanoparticles in C57Bl/6 Mouse Model of Multiple Sclerosis
title_full_unstemmed Prophylactic and Therapeutic Effects of MOG-Conjugated PLGA Nanoparticles in C57Bl/6 Mouse Model of Multiple Sclerosis
title_short Prophylactic and Therapeutic Effects of MOG-Conjugated PLGA Nanoparticles in C57Bl/6 Mouse Model of Multiple Sclerosis
title_sort prophylactic and therapeutic effects of mog conjugated plga nanoparticles in c57bl 6 mouse model of multiple sclerosis
topic multiple sclerosis
experimental autoimmune encephalomyelitis
myelin oligodendrocyte glycoprotein
poly (lactic-co-glycolic acid)
regulatory t cell
immune tolerance
biomaterials
url https://apb.tbzmed.ac.ir/PDF/apb-11-505.pdf
work_keys_str_mv AT mehrdadgholamzad prophylacticandtherapeuticeffectsofmogconjugatedplgananoparticlesinc57bl6mousemodelofmultiplesclerosis
AT husseinbaharlooi prophylacticandtherapeuticeffectsofmogconjugatedplgananoparticlesinc57bl6mousemodelofmultiplesclerosis
AT mehdishafieeardestani prophylacticandtherapeuticeffectsofmogconjugatedplgananoparticlesinc57bl6mousemodelofmultiplesclerosis
AT zeinabseyedkhan prophylacticandtherapeuticeffectsofmogconjugatedplgananoparticlesinc57bl6mousemodelofmultiplesclerosis
AT maryamazimi prophylacticandtherapeuticeffectsofmogconjugatedplgananoparticlesinc57bl6mousemodelofmultiplesclerosis