Abstract
Neurological disorders represent a major global health burden, primarily due to the limited ability of therapeutic agents to cross the blood-brain barrier (BBB). Nose-to-brain (NTB) delivery has emerged as a promising non-invasive strategy to bypass the BBB and directly target the central nervous system (CNS). Among various polymers, chitosan has gained significant attention owing to its favourable physicochemical properties, biocompatibility, biodegradability, mucoadhesive nature, and ability to transiently open tight junctions of the nasal epithelium. This review comprehensively discusses the potential of chitosan-based systems for NTB delivery in the management of neurological disorders. The article outlines the physicochemical properties and biomedical applications of chitosan, followed by a detailed discussion of nasal anatomy and transport pathways involved in NTB drug delivery. The pharmacological aspects of chitosan in neurological disorders are highlighted, including its anti-oxidative, anti-neuroinflammatory, anti-apoptotic, anti-excitotoxic effects, suppression of β-amyloid accumulation, and acetylcholinesterase inhibitory activity. Various formulation approaches are critically reviewed, including chitosan-based nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, liposomes, microparticles, microspheres, and in situ gels designed for intranasal administration. Furthermore, surface-modified chitosan systems aimed at enhancing brain targeting are discussed, such as PEGylation, ligand-conjugated chitosan (transferrin and lactoferrin), cell-penetrating peptide functionalization, thiolated chitosan, and pH-sensitive derivatives including carboxymethyl and N-trimethyl chitosan. Comparative tables summarize formulation strategies, neurological indications, biological models, key outcomes, and reported findings. Overall, this review highlights the significant potential of chitosan and its surface-engineered derivatives as versatile carriers for NTB delivery in neurological disorders.