Targeting inflammation with hyaluronic acid-based micro- and nanotechnology: A disease-oriented review

Inflammation is a pivotal immune response in numerous diseases and presents therapeutic challenges. Traditional anti-inflammatory drugs and emerging cytokine inhibitors encounter obstacles such as limited bioavailability, poor tissue distribution, and adverse effects. Hyaluronic acid (HA), a versatile biopolymer, is widely employed to deliver therapeutic agents, including anti-inflammatory drugs, genes, and cell therapies owing to its unique properties, such as hydrophilicity, biodegradability, and safety. HA interacts with cell receptors to initiate processes such as angiogenesis, cell proliferation, and immune regulation. HA-based drug delivery systems offer dual strategies for effective inflammation management, capitalizing on passive and active mechanisms. This synergy permits the mitigation of inflammation by lowering the doses of anti-inflammatory drugs and their off-target adverse effects. A diverse array of micro- and nanotechnology techniques enable the fabrication of tailored HA-engineered systems, including hydrogels, microgels, nanogels, microneedles, nanofibers, and 3D-printed scaffolds, for diverse formulations and administration routes. This review explores recent insights into HA pharmacology in inflammatory conditions, material design, and fabrication methods, as well as its applications across a spectrum of inflammatory diseases, such as atherosclerosis, psoriasis, dermatitis, wound healing, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, and colitis, highlighting its potential for clinical translation.