Nanoparticle-based Drug Delivery in Celiac Disease

Abstract

Celiac disease is a chronic autoimmune enteropathy triggered by the ingestion of dietary gluten in genetically predisposed individuals, resulting in the progressive atrophy of the intestinal villi. At present, the only standard of care is a strict, lifelong gluten-free diet, a treatment often compromised by inadvertent cross-contamination and associated nutritional deficiencies. Conventional oral therapeutics are rapidly degraded by gastric acids, face large transport barriers across the dense intestinal mucus layer, or induce dose-limiting systemic toxicities. This review discusses the role of engineered nanomedicines to overcome these physiological barriers for targeted therapeutic delivery. We review oral delivery systems, including luminally active silica nanocomposites for enzymatic degradation of immunogenic gluten peptides in the duodenum and multi-layered polymeric networks for localized gene delivery to intestinal epithelium to suppress local inflammatory cascades. We also examine intravenous platforms utilizing biodegradable nanoparticles designed to evade the mononuclear phagocyte system (MPS). These systemic carriers transport gluten antigens directly to antigen-presenting cells in the liver and spleen to induce antigen-specific immune tolerance. Current data demonstrate high efficacy in preclinical murine models, and proof-of-concept human clinical trial data (limited to the TAK-101 platform) show a significant reduction in gluten-driven inflammation and preservation of villous architecture. Finally, the translational trajectory for these therapeutics is discussed, emphasizing the manufacturing scale-up, long-term biocompatibility profiling, and the need for tailored pharmacokinetic modeling.