Central nervous system demyelinating diseases, represent a group of chronic autoimmune conditions
requiring long-term intervention. Traditional systemic administration methods face limitations due to the
blood-brain barrier, resulting in issues such as low central nervous system delivery efficiency, high systemic
exposure, and significant interindividual pharmacokinetic variability. These factors compromise treatment
precision and patient compliance. The Nose-to-Brain (N2B) route bypasses the blood-brain barrier via the
olfactory and trigeminal pathways, enabling direct central drug delivery with advantages including
non-invasiveness, high targeting specificity, and minimal systemic side effects. This study systematically
reviews the dual-pathway delivery mechanism of this route, along with recent advances in reducing
neuroinflammation, promoting myelin regeneration, and neuroprotective delivery strategies. It also analyzes
current challenges in clinical translation.
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