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.

Administration methods and dosage of poly(lactic acid)-glycol intervention to myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalitis mice

“…In addition, they demonstrated that intravenous administration resulted in the uptake of NLP by CD19-positive cells compared to subcutaneous injection, suggesting the tolerance mechanism may be mediated by circulation B cells. Another group reported that the MOG-conjugated PLGA nanoparticles in an EAE mouse model significantly increased IL-10 levels in cultured splenocytes [ 8 ]. Interestingly, Ovalbumin peptide-conjugated PLGA nanoparticles, used as a control group in this study, also significantly increased IL-10 levels compared to the naive group.…”

“…A larger number of mice could be used for a more detailed study. Second, based on the previous reports [ 3 , 8 ], we hypothesized that PLGA nanoparticles are nonspecifically taken up by B cells and could induce immune tolerance. However, we could not prove the pharmacokinetics of PLGA nanoparticles in detail, such as, to uptake into B cells or to deplete B cells and compare the difference in IL-10 levels in the study.…”

“…Polylactic-co-glycolic acid (PLGA) is an FDA-approved copolymer that can be polymerized to form capsules containing any active pharmaceutical ingredient and can be hydrolyzed to release its contents gradually [ 6 ]. PLGA conjugated with antigen is used to induce antigen-specific immune tolerance in mice, with and without immunosuppressive agents [ 3 , 7 , 8 ]. PLGA conjugated with MOG 35-55 was recently shown to tolerize MOG 35-55 EAE and reduce the severity of disease in a spatiotemporal fashion, requiring serial exposure to immunosuppressant/tolerizing agent rapamycin followed by the antigen [ 9 , 10 ].…”

PLGA Particles in Immunotherapy

“…Additionally, effects on immune homeostasis were reported in the form of increased populations of Tregs in the spleen. Ex vivo stimulation of the splenocytes resulted in lower secretion of pro-inflammatory IL-17 and IFN-γ but in turn increased IL-10 production [ 123 ]. A study from 2021 investigated an alternative to the co-delivery of tolerogenic adjuvants.…”

The Other Side of Plastics: Bioplastic-Based Nanoparticles for Drug Delivery Systems in the Brain

“…MS is known as a disease in which the immune system attacks the myelin sheath, an important component of axonal membranes, inducing progressive loss of neuronal structure and functions [163]. In this regard, recently Gholamzad et al developed PLGA-NPs conjugated with myelin oligodendrocyte glycoprotein (PLGA-MOG) [164]. These particles were then intravenously administered to a C57BL6 mouse model of MS. PLGA-MOG NPs were able to ameliorate clinical symptoms and autoimmune responses, reducing the infiltration of immune cells within the brain.…”