Remote loading of an autoantigen in PLGA nanoparticles for the treatment of multiple sclerosis

Autoimmune diseases like multiple sclerosis (MS) affect millions of people worldwide and have been growing in prevalence. Current therapeutic strategies either entirely suppress immune function or only offer modest efficacy. Research efforts have shifted focus more recently to antigen-specific therapies to promote immune tolerance and avoid compromising general immune function. Here, we show the application of a novel aqueous remote loading method using poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) to load myelin oligodendrocyte glycoprotein (MOG) peptide at high loading and encapsulation efficiency. MOG is a target of autoreactive T cells in MS. These NPs (750 ± 200 nm and - 16.7 ± 0.4 mV zeta potential) slowly and continuously released MOG peptide and decreased costimulatory molecule expression on dendritic cells in vitro. A single dose of MOG-PLGA NPs administered either SC or IV exerted strong efficacy in a murine experimental autoimmune encephalomyelitis (EAE) model of MS. Prophylactic treatment with MOG-PLGA NPs prevented disease progression, while therapeutic treatment with MOG-PLGA NPs effectively reversed the EAE symptoms. MOG-PLGA NPs also induced long term tolerance against EAE re-challenge. Mechanistically, a single injection of MOG-PLGA NPs induced a 2-fold increase in the frequency of MOG-specific CD4+ T regulatory cells (Tregs) and anergic T cells, compared with PBS or free MOG peptide control groups. Additionally, histopathological analysis demonstrated a positive correlation between % demyelination and EAE score. Hence, autoantigens, such as MOG peptide, can be remote loaded into PLGA NPs from an aqueous solution at high loading and encapsulation efficiency for long-term controlled release.