Chitosan-coated solid lipid nanoparticles for nose-to-brain drug delivery: A comprehensive review

Background: The blood-brain barrier (BBB) limits the effectiveness of treatment of several central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease, schizophrenia, and bipolar disorder. Because of this limitation, intranasal drug delivery is an effective, non-invasive way to bypass the BBB via the olfactory and trigeminal pathways. Methodology: In this review, we critically evaluate the design, characterization, mechanism of action, and potential therapeutic use of Chitosan-coated Solid Lipid Nanoparticles (SLNs) as a delivery system for drugs from the nasal cavity to the brain. A structured literature search was conducted in PubMed, Scopus, and Web of Science for studies published between 2019 and 2025 using keywords related to chitosan-coated solid lipid nanoparticles and nose-to-brain delivery. Studies reporting pharmacokinetic parameters, such as brain AUC, brain-targeting efficiency (BTE%), and drug-targeting index (DTI), were included. Results and Discussion: Preclinical studies show that some chitosan-coated SLN formulations significantly improve drug pharmacokinetics, increasing the brain area under the curve (AUC) compared with conventional formulations. Reported brain targeting efficiency (BTE%) with drug targeting index (DTI) values confirmed preferential nose-to-brain transport and improved CNS exposure. The improved targeting efficiency is attributed to the mucoadhesive nature of chitosan, enhanced permeability, and prolonged nasal residence time of SLNs. Conclusion: Chitosan-coated Solid Lipid Nanoparticles (SLNs) are an interesting candidate for a nanocarrier system to deliver drugs through the intranasal route into the CNS (Central Nervous System). Future research should emphasize Quality by Design (QbD)-based optimization, advanced surface modifications for targeted delivery, and comprehensive safety and clinical validation to support successful translation into clinical practice.