الفهرس 
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Abstract
Multiple sclerosis (MS) is the most common autoimmune disorder affecting the central nervous system and its pathological hallmarks are plaques of demyelination in the CNS, with surrounding area of inflammation and neurodegeneration. Different histological studies demonstrated that the hippocampus is extensively involved during MS. Remyelination process, which restores the support of axons represents an important strategy in demyelinating disorders, where neuroprotection may be enhanced.
Macrophages and microglia have long been recognized for their ability to dynamically respond to stimuli in their microenvironment. They can modulate their phenotypes in response to extracellular cues, either as M1 (pro-inflammatory) phenotype which is a source of many cytotoxic substances, such as the pro-inflammatory cytokine, TNF-α, inducible nitric oxide synthase (iNOS) or M2 (anti-inflammatory) Arginase-1+.
One particular microRNA, miRNA-155 plays a critical role in hematopoietic cell development and tightly regulates innate and adaptive immune responses in response to infection. In primary cultured microglia, miRNA-155 is the most significantly upregulated miRNA under inflammatory M1-skewing conditions. Inhibition of miR-155 decreased the release of pro-inflammatory cytokines and nitric oxide in microglial cultures, and the conditioned medium from these microglia could decrease neuronal cell death. At the same time silencing of miRNA-155 in animal models of demyelination resulted in suppression of inflammation and clinical improvement.
However, several challenges have to be overcome for successful clinical translation of these therapeutic agent. Susceptibility of RNAs to degradation by nucleases, their stability, their poor cellular uptake, or the nonspecific delivery of miRNA molecules are some of these challenges. In last years, PLGA nanoparticles becomes one of the most studied polymers in non-viral microRNA delivery, on account of several unique attributes: its polycationic nature, biodegradability and biocompatiblity. In the current study anti-miR-155 PLGA/PEI nanoparticles were synthesized and characterized using Transmission Electric Microscope (TEM) and Malvern zetasizer. This was followed by an in-vitro study on Bone Marrow Derived Macrophages (BMDMs) which proved the the efficacy of silencing of miRNA-155 using PLGA/PEI nanoparticles on decreasing macrophages viability.