Polymeric bile acid (pBA) nanoparticles and tolerogenic formulation containing polymeric bile acid nanoparticles for oral delivery and induction of antigen-specific tolerance in a subject may include immunosuppressants and/or disease-specific antigen. Oral delivery results in local organ accumulation as well as systemic delivery of the nanoparticles. Early intervention with the nanoparticles induces antigen-specific tolerance and prevents development of autoimmune disorders. Treatment with the nanoparticles results in long-term antigen-specific immune tolerance, even after cessation of treatment, in autoimmune diseases.