Targeted-Immunomodulatory Nanomedicines for the Treatment of Autoimmune Diseases via Multiple Administration Routes.

The incidence and prevalence of autoimmune diseases are rising globally, presenting a significant health challenge. Current treatments focus on symptom management and immunosuppression, often resulting in side-effects such as increased infection risk and broad immunosuppression. Targeted immune modulation strategies, particularly through nanomedicines, offer promising advancements by enabling precise drug delivery and reducing systemic toxicity, risks, and pharmacokinetic issues. Nanocarriers, which are nanoparticles with drugs encapsulated, improve targeting to inflamed areas and lymphoid tissues, protecting therapeutic agents from degradation. Administration routes-intravenous, subcutaneous, intramuscular, and oral-offer distinct benefits for enhancing efficacy in treating autoimmune diseases. In this review, we explore autoimmune diseases and review the limitations of current treatment options. We also emphasize the importance of exploring various administration routes for innovative nanocarrier systems and discuss their effects on modulating immune responses and inducing immune tolerance in autoimmune diseases. In particular, we highlight numerous preclinical studies utilizing intravenous, subcutaneous/intramuscular, and oral nanocarrier formulations that demonstrate substantial improvements in therapeutic efficacy and dose reduction compared to conventional therapies, underscoring the translational potential of nanomedicines for autoimmune diseases. Finally, we discuss future research directions and challenges in the development of nanomedicines for autoimmune diseases.