Nose-to-Brain Nanocarrier Delivery for Neurodegenerative Diseases: From Anatomical Pathways and Biological Barriers to Brain-Targeting Evidence and Clinical Translation
Year: 2026
Type: article
Abstract: Central nervous system (CNS) disorders are difficult to treat because traditional oral or parenteral delivery often fails to deliver sufficient quantities of therapeutic compounds to the brain. Major challenges include limited drug permeability, systemic toxicity, enzymatic degradation, and the blood–brain barrier (BBB). Because the nasal canal is physically related to the brain through olfactory and trigeminal pathways, intranasal delivery has drawn attention as a non-invasive method. By boosting drug solubility, shielding labile molecules, extending nasal residency, and regulating drug release, nanocarriers may further enhance this pathway. CNS delivery has been studied using polymeric nanoparticles, PLGA and chitosan systems, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, micelles, nanogels, and biomimetic systems. However, care must be used when interpreting nose-to-brain research. Because systemic absorption, enhanced stability, and extended nose residency might potentially increase brain exposure, increased brain concentration following intranasal delivery does not by itself demonstrate direct neural transport. The anatomical routes, physiological hurdles, nanocarrier techniques, and applications in Parkinson's disease (PD) and Alzheimer's disease (AD) are summarized in this critical review, with a focus on brain-targeting assessment, safety, manufacturing, and regulatory issues. Significant preclinical potential is shown by current data; nonetheless, effective clinical translation necessitates repeatable nasal deposition, suitable controls, regional brain analysis, long-term safety evaluation, scalable production, and proof of significant therapeutic efficacy.
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223567207