EMERGING NOSE-TO-BRAIN DRUG DELIVERY STRATEGIES FOR AMYOTROPHIC LATERAL SCLEROSIS: A PROMISING FRONTIER IN NEUROTHERAPEUTICS
DOI:
https://doi.org/10.22159/ijap.2026v18i2.56993Keywords:
ALS (amyotrophic lateral sclerosis), Neurotherapeutics, Nose-to-brain delivery, Olfactory pathway, NanocarriersAbstract
The progressive neurodegenerative illness known as amyotrophic lateral sclerosis is characterized by the death of motor neurons, which causes paralysis, muscle atrophy, and ultimately fatal respiratory failure. Despite advances in understanding its molecular pathology, currently approved therapies such as Riluzole and Edaravone offer only modest clinical benefits, largely due to limited central nervous system exposure. The blood–brain barrier remains a major challenge for effective drug delivery to neural targets. In this context, intranasal nose-to-brain delivery has emerged as a promising non-invasive strategy to bypass the blood–brain barrier via olfactory and trigeminal neural pathways, enabling direct drug transport to the brain while reducing systemic exposure. Recent preclinical studies have explored a range of nanocarrier-based systems, including polymeric nanoparticles, lipid-based carriers, nanoemulsions, and hybrid formulations, to enhance nasal residence time, epithelial uptake, and neuronal transport. Functionalization with targeting ligands and mucoadhesive components has further improved brain targeting efficiency and therapeutic retention. However, challenges related to formulation complexity, long-term safety, scalability, and clinical translation remain unresolved. This review critically evaluates recent advances in nanocarrier-mediated nose-to-brain delivery for amyotrophic lateral sclerosis, highlighting current limitations and future directions required for successful clinical application.
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