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

Abstract

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.