Nanoformulated Recombinant Human Myelin Basic Protein and Rituximab Modulate Neuronal Perturbations in Experimental Autoimmune Encephalomyelitis in Mice

Introduction: Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBPRTX) was prepared and investigated in comparison...

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Published inInternational journal of nanomedicine Vol. 17; pp. 3967 - 3987
Main Authors Saad, Muhammed A, Eissa, Noha M, Ahmed, Mohammed A, ElMeshad, Aliaa N, Laible, Götz, Attia, Ahmed S, Al-Ghobashy, Medhat A, Abdelsalam, Rania M, Al-Shorbagy, Muhammad Y
Format Journal Article
LanguageEnglish
Published Macclesfield Dove Medical Press Limited 01.01.2022
Taylor & Francis Ltd
Dove
Dove Medical Press
Subjects
Acids
Analysis
Antibodies
Antigens
Biological response modifiers
Blood-brain barrier
Brain research
Chromatography
Disease
Drug delivery systems
Drugs
Encephalomyelitis
experimental autoimmune encephalomyelitis
FDA approval
Immunotherapy
Interferon
Interleukins
Laboratory animals
Mice
Monoclonal antibodies
Multiple sclerosis
Myelin proteins
nanoparticle
Nanoparticles
Neurons
Optimization
Original Research
Particle size
Pathogenesis
Pharmacy
Polyvinyl alcohol
Proteins
recombinant human myelin basic protein
rituximab
Targeted cancer therapy
Transforming growth factors
Egypt
United States > US
Online AccessGet full text
ISSN1178-2013
1176-9114
1178-2013
DOI10.2147/IJN.S359114

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Abstract Introduction: Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBPRTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuroprotective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE). Methods: EAE was induced in the corresponding mice by injecting 100 [micro]L of an emulsion containing complete Freund's adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-[gamma] (IFN-[gamma]), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-[alpha]), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2', 3' cyclic nucleotide 3' phosphodiesterase (CNP) and transforming growth factor beta (TGF-[beta]) along with some histopathological analyses. Results: The results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-[beta] was also noticed along with marked decline in the levels of NF-kB and TNF-[alpha]. Conclusion: Nano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination. Keywords: multiple sclerosis, experimental autoimmune encephalomyelitis, nanoparticle, rituximab, recombinant human myelin basic protein
AbstractList Muhammed A Saad,1,2 Noha M Eissa,2 Mohammed A Ahmed,3 Aliaa N ElMeshad,3,4 Götz Laible,5– 7 Ahmed S Attia,8 Medhat A Al-Ghobashy,9,10 Rania M Abdelsalam,1,2 Muhammad Y Al-Shorbagy1,11 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2School of Pharmacy, Newgiza University, Giza, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Faculty of Nanotechnology for Postgraduate Studies, Cairo University, Giza, Egypt; 5AgResearch, Ruakura Research Centre, Hamilton, New Zealand; 6School of Medical Sciences, University of Auckland, Auckland, New Zealand; 7Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand; 8Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 9Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 10Bioanalysis Research Group, School of Pharmacy, Newgiza University, Giza, Egypt; 11Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Ahmed S Attia, Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt, Email ahmed.attia@pharma.cu.edu.egIntroduction: Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBP-RTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuro-protective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE).Methods: EAE was induced in the corresponding mice by injecting 100 μL of an emulsion containing complete Freund’s adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2’, 3’ cyclic nucleotide 3’ phosphodiesterase (CNP) and transforming growth factor beta (TGF-β) along with some histopathological analyses.Results: The results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-β was also noticed along with marked decline in the levels of NF-kB and TNF-α.Conclusion: Nano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination.Keywords: multiple sclerosis, experimental autoimmune encephalomyelitis, nanoparticle, rituximab, recombinant human myelin basic protein
Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBP-RTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuro-protective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE).IntroductionRituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBP-RTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuro-protective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE).EAE was induced in the corresponding mice by injecting 100 μL of an emulsion containing complete Freund's adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2', 3' cyclic nucleotide 3' phosphodiesterase (CNP) and transforming growth factor beta (TGF-β) along with some histopathological analyses.MethodsEAE was induced in the corresponding mice by injecting 100 μL of an emulsion containing complete Freund's adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2', 3' cyclic nucleotide 3' phosphodiesterase (CNP) and transforming growth factor beta (TGF-β) along with some histopathological analyses.The results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-β was also noticed along with marked decline in the levels of NF-kB and TNF-α.ResultsThe results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-β was also noticed along with marked decline in the levels of NF-kB and TNF-α.Nano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination.ConclusionNano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination.
Introduction: Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBP-RTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuro-protective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE). Methods: EAE was induced in the corresponding mice by injecting 100 μL of an emulsion containing complete Freund’s adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2’, 3’ cyclic nucleotide 3’ phosphodiesterase (CNP) and transforming growth factor beta (TGF-β) along with some histopathological analyses. Results: The results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-β was also noticed along with marked decline in the levels of NF-kB and TNF-α. Conclusion: Nano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination.
Introduction: Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBPRTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuroprotective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE). Methods: EAE was induced in the corresponding mice by injecting 100 [micro]L of an emulsion containing complete Freund's adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-[gamma] (IFN-[gamma]), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-[alpha]), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2', 3' cyclic nucleotide 3' phosphodiesterase (CNP) and transforming growth factor beta (TGF-[beta]) along with some histopathological analyses. Results: The results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-[beta] was also noticed along with marked decline in the levels of NF-kB and TNF-[alpha]. Conclusion: Nano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination. Keywords: multiple sclerosis, experimental autoimmune encephalomyelitis, nanoparticle, rituximab, recombinant human myelin basic protein
Audience Academic
Author Ahmed, Mohammed A
Abdelsalam, Rania M
Laible, Götz
Al-Ghobashy, Medhat A
Al-Shorbagy, Muhammad Y
Saad, Muhammed A
ElMeshad, Aliaa N
Eissa, Noha M
Attia, Ahmed S
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Snippet Introduction: Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis...
Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this...
Muhammed A Saad,1,2 Noha M Eissa,2 Mohammed A Ahmed,3 Aliaa N ElMeshad,3,4 Götz Laible,5– 7 Ahmed S Attia,8 Medhat A Al-Ghobashy,9,10 Rania M Abdelsalam,1,2...
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StartPage 3967
SubjectTerms Acids
Analysis
Antibodies
Antigens
Biological response modifiers
Blood-brain barrier
Brain research
Chromatography
Disease
Drug delivery systems
Drugs
Encephalomyelitis
experimental autoimmune encephalomyelitis
FDA approval
Immunotherapy
Interferon
Interleukins
Laboratory animals
Mice
Monoclonal antibodies
Multiple sclerosis
Myelin proteins
nanoparticle
Nanoparticles
Neurons
Optimization
Original Research
Particle size
Pathogenesis
Pharmacy
Polyvinyl alcohol
Proteins
recombinant human myelin basic protein
rituximab
Targeted cancer therapy
Transforming growth factors
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Title Nanoformulated Recombinant Human Myelin Basic Protein and Rituximab Modulate Neuronal Perturbations in Experimental Autoimmune Encephalomyelitis in Mice
URI https://www.proquest.com/docview/2715159264
https://www.proquest.com/docview/2714656966
https://pubmed.ncbi.nlm.nih.gov/PMC9464642
https://doaj.org/article/82b770e954594d7194f89cf705dfd027
Volume 17
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