Neuroprotective and Antioxidant Effect of Naringenin-Loaded Nanoparticles for Nose-to-Brain Delivery

Naringenin is a naturally occurring flavanone present in citrus fruits and is extensively studied for its antioxidant, anti-inflammatory, and neuroprotective properties. Its advancement as a therapeutic compound is restricted by poor water solubility and limited bioavailability. Intranasal delivery from the nose to the brain is being investigated as a non-invasive approach that might enhance access to the central nervous system via olfactory and trigeminal pathways, thereby decreasing reliance on systemic transport through the blood-brain barrier. This review outlines the characteristics of naringenin, the justification for utilizing nanoparticle delivery, relevant carrier systems, and existing preclinical evidence. Chitosan nanoparticles, nanoemulsions, lipid carriers with nanostructures, and cubosomal systems have been explored in experimental research. A 2019 research found that naringenin-loaded chitosan nanoparticles had an average size of about 87.6 nm and improved nasal absorption in tests conducted in the lab. A study in 2025 indicated that chitosan nanoparticles enhanced ex vivo permeation and cognitive results in a model with experimental animals. These results are encouraging but still preclinical; they do not demonstrate clinical efficacy in humans. The evaluation further differentiates research formulations from commercial products. In the reviewed literature and sources, no approved naringenin-loaded intranasal nanoparticle product for commercial sale was found. Additional efforts are required for nasal safety, dose uniformity, long-term stability, scalable production, and regulated clinical assessment.