Biomaterial-based local drug delivery in autoimmune and immune-mediated inflammatory diseases: An exposure-centric...

Autoimmune and immune-mediated inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis, often demonstrate incomplete responses to systemic therapies. This limitation may reflect not only insufficient pharmacological potency but also inadequate control of drug exposure at the site of action. While upstream immune activation is frequently systemic, tissue injury is influenced by compartmentalized effector processes, highlighting the importance of spatial and temporal drug distribution within diseased tissues. Biomaterial-based delivery systems, including hydrogels, nanoparticles, lipid carriers, microneedles, and hybrid constructs, are increasingly recognized not only as drug transport vehicles but also as modulators of local exposure. Their therapeutic performance is shaped by disease-specific biological barriers, including synovial compartmentalization in rheumatoid arthritis, mucosal transport limitations in inflammatory bowel disease, and epidermal constraints in psoriasis. Stimuli-responsive systems may further enable context-dependent modulation of drug availability, although their impact on clinically relevant exposure metrics remains insufficiently defined. Unlike many previous reviews that have largely organized biomaterial systems according to carrier type, therapeutic cargo, or delivery platform, this review interprets existing strategies through the lens of local exposure and disease-specific exposure limitations. However, current evidence supporting local exposure optimization remains heterogeneous, ranging from direct pharmacokinetic measurements to imaging-based localization and pharmacodynamic inference. This narrative review provides an exposure-centric perspective by integrating local concentration, tissue distribution, and exposure duration to reinterpret current biomaterial-based strategies in autoimmune and immune-mediated inflammatory diseases. By linking disease-specific exposure constraints with delivery design principles, this perspective supports more rational exposure-informed development of localized immunomodulatory therapies.