Chitosan-Based Nanoparticles for Nose-to-Brain Drug Delivery: A Real Path toward Effective CNS Therapy?

Treating central nervous system (CNS) disorders remains a major clinical challenge. The blood-brain barrier (BBB), systemic toxicity, and first-pass metabolism are key obstacles. These factors limit the effective drug delivery to the brain. Intranasal administration has emerged as a noninvasive strategy to bypass the BBB. This approach enables direct drug delivery to the brain through the olfactory and trigeminal nerve pathways, commonly referred to as nose-to-brain (N2B) delivery. In this context, chitosan (CS), a biocompatible and mucoadhesive polysaccharide with permeation-enhancing properties, has gained significant interest as a functional material for nanoparticle (NP) engineering. CS-based or CS-coated NP can prolong the residence time on the nasal mucosa and facilitate drug transport to the CNS. This review provides a comprehensive overview of recent advances in CS-based NP for N2B drug delivery across a range of CNS disorders, including neurodegenerative, neuropsychiatric, neoplastic, and infectious conditions. Particular attention is given to formulation strategies, mechanistic insights, and preclinical outcomes. Recent patent applications are surveyed to underscore the translational potential and commercial interest in this technology. Collectively, CS-based NPs effectively address major therapeutic barriers, establishing a transformative and innovative platform in CNS drug delivery.