Antioxidant Polymeric and Non-Polymeric Nanoformulations for the Treatment of Autoimmune Diseases

Autoimmune diseases are characterized by chronic inflammation, immune dysregulation, and excessive oxidative stress, which collectively contribute to a progressive tissue damage and organ dysfunction. Although conventional immunosuppressive and anti-inflammatory therapies remain the main therapeutic approach, their clinical efficacy is often limited by poor pharmacokinetic properties, low tissue selectivity, systemic toxicity, and adverse effects following long-term administration. In this context, antioxidant-based nanoformulations have emerged as promising multi-target therapeutic strategies for the modulation of oxidative and inflammatory pathways involved in autoimmune disorders. This review focuses on polymeric and non-polymeric nanoformulations designed to improve the solubility, stability, bioavailability, controlled release, and targeted delivery of antioxidant and anti-inflammatory agents for autoimmune disease treatment. Recent advances in nanocarrier systems applications, including nanogels, poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), polymethacrylate, chitosan, hyaluronic acid, hydroxyapatite (HAP), lipid-based and ROS-responsive nanosystems, are discussed. The therapeutic potential of nanoencapsulated steroidal and non-steroidal anti-inflammatory drugs, antioxidant compounds, enzymes, inorganic elements, and nucleic acid-binding systems is evaluated through preclinical and limited clinical evidence. Many of these reported nanoformulations exhibit enhanced therapeutic efficacy, improved tissue targeting, reduced systemic toxicity, and the ability to simultaneously modulate oxidative stress and inflammatory signaling pathways. Despite the encouraging findings, important challenges remain regarding clinical translation, long-term safety, reproducibility, and large-scale production. In overall, antioxidant nanoformulations represent a promising and evolving platform for the development of more effective and targeted therapies against autoimmune diseases.