Drug Delivery Strategies for Tolerogenic Therapy for Autoimmune Diseases in an Antigen-Specific Manner

Abstract

Autoimmune diseases are the result of an improper immune response towards a self-antigen. Predominantly, autoimmune diseases have been treated using therapies that suppress systemic immune responses, which can result in significant side-effects like increased risk of infection and cancer. Alternatively, induction of immune tolerance through antigen-specific therapies can inhibit disease-associated responses without systemic suppression. Previously, immune tolerance has been accomplished by soluble antigen delivery through oral, nasal or sublingual routes. However, these therapies have shown minimal success in clinical settings. In an attempt to increase the efficacy of these therapies, recent work has utilized microparticulate delivery vehicles for the induction of immune tolerance. Microparticles are capable of increasing the solubility and circulation of cargo. In addition, their ability to passively target macrophages and dendritic cells increases their capacity for modulating the immune response. Recent work has shown microparticles fabricated with disease-associated antigens have limited disease progression and severity in animal models of Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis. Inhibition of disease progression has corresponded with an antigen-specific decrease in inflammatory responses. The emerging field of inducing tolerance through microparticle-based therapies can limit therapeutic side-effects and increase patient quality of life by providing for long-term suppression of autoimmune disorders without compromising systemic immune function.