Nanoscience in Multiple Sclerosis (original) (raw)
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Scope and Applications of Nanomedicines for the Management of Multiple Sclerosis
Current Drug Metabolism, 2015
Neuropathic pain, resultant from the dysfunction of the peripheral and central 16 nervous system occurs in a variety of pathological conditions including trauma, diabetes, cancer, 17 HIV, surgery, multiple sclerosis, ischemic attack, alcoholism, spinal cord damage, and many 18 others. Despite the availability of various treatment strategies, the percentage of patients 19 achieving adequate pain relief remains low. The clinical failure of most effective drugs is often 20 not due to a lack of drug efficacy but due to the dose-limiting central nervous system (CNS) 21 toxicity of the drugs that preclude dose escalation. There is a need for cross-disciplinary 22 collaborations, to meet these challenges. In this regard, the integration of nanotechnology with 23 neuroscience is one of the most important fields. In recent years, promising pre-clinical research
Nanomaterial Applications in Multiple Sclerosis Inflamed Brain
Journal of Neuroimmune Pharmacology, 2015
Nanomaterials interact with cells and modify their function and biology. Manufacturing this ability can provide tissue-engineering scaffolds with nanostructures able to influence tissue growth and performance. Carbon nanotube compatibility with biomolecules motivated ongoing interest in the development of biosensors and devices including such materials. More recently, carbon nanotubes have been applied in several areas of nerve tissue engineering to study cell behavior or to instruct the growth and organization of neural networks. To gather further knowledge on the true potential of future constructs, in particular to assess their immunemodulatory action, we evaluate carbon nanotubes interactions with human dendritic cells (DCs). DCs are professional antigen-presenting cells and their behavior can predict immune responses triggered by adhesion-dependent signaling. Here, we incorporate DC cultures to carbon nanotubes and we show by phenotype, microscopy, and transcriptional analysis that in vitro differentiated and activated DCs show when interfaced to carbon nanotubes a lower immunogenic profile.
international journal of nano dimension, 2016
Several MRI contrast agents (CAs) are used in medical diagnosis that gadolinium (Gd3+) is the most widely used as contrast agents. Unfortunately, its toxicity is due to its inefficiency. In this review, we discuss about the ability of SPIONs in MRI and application in Multiple Sclerosis diagnosis. Superparamagnetic iron oxide nanoparticles (SPIONs) such as magnetite nanoparticles are used as good CAs in recent years because of biocompatibility, low level of toxicity, magnetic properties, simple synthesis and coating to use in medical diagnosis. Uncoated magnetite nanonoparticles are insoluble in water. Hydrophilic coatings result water solubility of nanoparticles and prolonged circulation half-lives of SPION and reduce recognition by RES. SPIONs have an important role in diagnosis of multiple sclerosis (MS) by MRI. SPIONs are MRI contrast agents better than gadolinium because, SPIONs taken up by macrophages but not Gd-nanoparticles.
Progress in nanotechnology has determined new strategies concerning drug delivery into the central nervous system for the treatment of degenerative and inflammatory diseases. To date, brain targeting through systemic drug administration, even in a nano-composition, is often unsuccessful. Therefore, we investigated the possibility of loading T lymphocytes with PGLA–PEG COOH magnetite nanoparticles (30 nm), which can be built up to easily bind drugs and monoclonal antibodies, and to exploit the ability of activated T cells to cross the blood–brain barrier and infiltrate the brain parenchyma. Iron oxide nanoparticles have been widely used in biomedical applications due to their theranostic properties and are therefore a well-established nanomaterial. The magnetite core is easily hybridized with polymeric compounds that may enhance the possibility of the nanoparticles entering cells with low phagocytic properties. Taking advantage of these material characteristics, after in vitro assessment of the viability and functionality of nano-loaded MOG 35–55 specific T cells, we transferred cells containing the nano-cargo into nä ıve mice affected by experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. By means of histological and immunohistological methods, we were able to identify the nano-loaded T cells in the central nervous system. Our data demonstrated that T cells containing nanomaterials hold the possibility of carrying and releasing nanoparticles in the brain.
Proceedings of the National Academy of Sciences, 2012
The immune response is normally controlled by regulatory T cells (Tregs). However, Treg deficits are found in autoimmune diseases, and therefore the induction of functional Tregs is considered a potential therapeutic approach for autoimmune disorders. The activation of the ligand-activated transcription factor aryl hydrocarbon receptor by 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or other ligands induces dendritic cells (DCs) that promote FoxP3+Treg differentiation. Here we report the use of nanoparticles (NPs) to coadminister ITE and a T-cell epitope from myelin oligodendrocyte glycoprotein (MOG)35–55to promote the generation of Tregs by DCs. NP-treated DCs displayed a tolerogenic phenotype and promoted the differentiation of Tregs in vitro. Moreover, NPs carrying ITE and MOG35–55expanded the FoxP3+Treg compartment and suppressed the development of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis. Thus, NPs are po...
Nano- and micro-based systems for immunotolerance induction in multiple sclerosis
Human Vaccines & Immunotherapeutics, 2016
It is estimated that more than 2.5 million individuals worldwide have multiple sclerosis (MS). MS is an autoimmune neurodegenerative disease resulting from the destruction of the myelin sheath that enwraps axons driven by an immune cell attack to the central nervous system. Current therapeutic programs for MS focus in immunosuppression and more recently in the use of immunomodulatory molecules. These therapeutic approaches provide significant improvements in the management of the disease, but are frequently associated with an increased susceptibility of opportunistic infection. In this commentary, we highlight the application of nano and micro-technologies as emerging and innovative solutions for MS therapy with the potential to restore immune homeostasis via antigen-specific interactions. Furthermore, we propose and discuss the usage of a minimally invasive approach, namely microneedle patches, as a new therapeutic route. Microneedle patches for the delivery of specific antigens to restore immunotolerance in the context of Multiple Sclerosis.
Indian Journal of Pharmaceutical Sciences
Ojha et al.: Development of Dimethyl Fumarate-loaded Chitosan Nanoparticles The aim of the present study was to access the potential of dimethyl fumarate-loaded chitosan polymeric nanoparticles for the management of multiple sclerosis. Dimethyl fumarate-loaded chitosan nanoparticles were prepared by polyelectrolyte complex coaservation technique. The prepared nanoparticles were characterized and found to have an average particle size of 324 nm, zeta potential of-34.85 mV and a poly dispersity index of 0.367. The entrapment effi ciency was found to be 65.36 % and the drug loading was 28 %. The formulation's in vitro drug release profi le and stability parameters were also evaluated. Cumulative percent drug release was found to be 84 % up to 24 hours and the formulation was found to be stable at 28° for 90 days. In vitro neuroprotective effect of the nanoformulation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on human neuroblast SH-SY5Y cells and the treated cells showed improved cell viability under hydrogen peroxide-induced cell apoptosis. In vivo cuprizone model for multiple sclerosis in rodents also confi rmed these fi ndings by showing a signifi cant increase in locomotion score.
Nanoparticle-Based Technology Approaches to the Management of Neurological Disorders
International Journal of Molecular Sciences, 2020
Neurological disorders are the most devastating and challenging diseases associated with the central nervous system (CNS). The blood-brain barrier (BBB) maintains homeostasis of the brain and contributes towards the maintenance of a very delicate microenvironment, impairing the transport of many therapeutics into the CNS and making the management of common neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cerebrovascular diseases (CVDs) and traumatic brain injury (TBI), exceptionally complicated. Nanoparticle (NP) technology offers a platform for the design of tissue-specific drug carrying systems owing to its versatile and modifiable nature. The prospect of being able to design NPs capable of successfully crossing the BBB, and maintaining a high drug bioavailability in neural parenchyma, has spurred much interest in the field of nanomedicine. NPs, which also come in an array of forms including polymeric NPs, solid lipid nanoparticles (SLNs), quantum...
Journal of controlled release : official journal of the Controlled Release Society, 2017
Glucocorticoids (GC) are widely used to treat acute relapses in multiple sclerosis (MS) patients, but their application is accompanied by side effects due to their broad spectrum of action. Here, we report on the therapeutic option to apply GC via inorganic-organic hybrid nanoparticles (IOH-NP) with the composition [ZrO](2+)[(BMP)0.9(FMN)0.1](2-) (designated BMP-NP with BMP: betamethasone phosphate; FMN: flavinmononucleotide). We found that these BMP-NP have an increased cell type-specificity compared to free GC while retaining full therapeutic efficacy in a mouse model of MS. BMP-NP were preferentially taken up by phagocytic cells and modulated macrophages in vivo more efficiently than T cells. When GC were applied in the form of BMP-NP, treatment of neuroinflammatory disease in mice exclusively depended on the control of macrophage function whereas effects on T cells and brain endothelial cells were dispensable for therapeutic efficacy. Importantly, BMP-NP were not only active in ...
2011
Neuroinflammation have been described in a increasing number of central and peripheral nervous system disorders, with different pathogenesis and clinical phenotypes. In this paper, demyelinating diseases are focused, in a perspective of correlating pathogenesis with immunotherapy. Clinical characteristics and the underlying pathological processes of this striking group of neuroimmunological diseases are reviewed, highlighting their major distinguishing features. The classical pharmacological treatments are thoroughly described and compared, including the new upcoming drugs currently in the pipeline of practitioners. Some examples are given with respect to novel formulations based on nanoparticles already tested for the discussed drugs.