Co‐Delivery of Disease Associated Peptide and Rapamycin via Acetalated Dextran Microparticles for Treatment of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system. While 2.5 million people are affected by MS worldwide, there is no cure other than ameliorating the symptoms through broad immune suppression, which leads to side effects, including increased risks of infection and cancer development. Therefore, tolerance induction specific to disease‐associated antigens serves as a promising alternative as it inhibits disease progression without sacrificing immune competence. In this study, the authors show the efficacy of acetalated dextran (Ace‐DEX) microparticles (MPs) as a potential MS treatment. Ace‐DEX MPs encapsulating ovalbumin (OVA) and the immunosuppressant rapamycin (Rapa) substantially inhibits the inflammation in OVA‐induced delayed‐type hypersensitivity reactions. When tested as a therapeutic treatment for experimental autoimmune encephalomyelitis, the mouse model for MS, MPs containing Rapa, and disease‐associated proteolipid protein (PLP) (Rapa/PLP/MPs) inhibits disease progression, lowers the clinical score, and suppresses the production of inflammatory cytokines (e.g., interferon gamma, interleukin‐17A, and granulocyte‐macrophage colony‐stimulating factor) in splenocytes isolated from treated mice. Rapa/PLP/MPs in vitro also promotes Foxp3 expression, inhibits pro‐inflammatory cytokine production, and dampens T cell proliferation, suggesting the differentiation of antigen‐specific regulatory T cells. Together these data illustrate the promise of a MS treatment using a polymeric particulate delivery platform via the induction of antigen‐specific T cell tolerance.