Chitosan-Coated Quercetin Lipid Nanoparticles for Intranasal Brain Delivery: A Short Review

Quercetin is a dietary flavonol with well-documented antioxidant and anti-inflammatory activity, and recent studies show that it can also lower amyloid burden, oxidative stress and neuroinflammation in animal models of Alzheimer's disease, Parkinson's disease and stress-related disorders. Its clinical use is limited by very low aqueous solubility (about 0.01 mg/mL), extensive intestinal and hepatic conjugation, and poor access to the brain across the blood–brain barrier. The intranasal route can deliver drugs to the brain along the olfactory and trigeminal nerves and bypasses hepatic first-pass metabolism, but mucociliary clearance removes most conventional nasal formulations within about 10 to 20 minutes. Lipid nanoparticles, particularly nanostructured lipid carriers (NLCs), solubilise lipophilic drugs and protect them from degradation, and coating them with the cationic polysaccharide chitosan adds mucoadhesion and a transient opening of tight junctions. Dispersing the coated particles in a thermosensitive in situ gel can extend residence time further. This short review draws on open online literature to describe the biopharmaceutical problem, the nose-to-brain pathways, lipid nanoparticle design, the intranasal quercetin nanocarriers reported so far, the rationale for chitosan functionalisation, in situ gelling vehicles, and a quality-by-design strategy using a three-factor Box–Behnken design. A staged evaluation plan covering physicochemical, in vitro, ex vivo, safety, stability and in vivo studies is proposed. No study identified in this review combined statistical optimisation, chitosan surface functionalisation of a lipid carrier, quantitative mucoadhesion and ciliotoxicity testing, and an in situ gel for quercetin in one integrated programme, and this gap is the main opportunity identified.