Nanomedicines for Neurodegenerative Ageing: Nasal Delivery Innovations for Alzheimer’s and Parkinson’s Disease

Alzheimer's disease and Parkinson's disease are progressive, age-related neurodegenerative disorders with increasing global prevalence, yet their treatment remains challenging despite the availability of multiple therapeutic agents. Conventional formulations are often limited by poor solubility, restricted blood-brain barrier penetration, extensive first-pass metabolism, short elimination half-life, low brain bioavailability, and systemic adverse effects. In recent years, the nose-to-brain route has emerged as a promising strategy for delivering therapeutics directly to the brain. This approach offers non-invasive administration, rapid onset of action, direct brain targeting via olfactory and trigeminal pathways, reduced systemic exposure, bypassing of first-pass metabolism, improved bioavailability, and enhanced patient compliance. To exploit these advantages, a variety of biodegradable nanocarrier systems have been investigated, including lipid-based and polymer-based nanoparticles, nasal gel-based systems, nanoemulsions, nanosuspensions, hybrid nanoparticles, and nasal sprays. This review provides a comprehensive synthesis of preclinical studies evaluating nose-to-brain nanocarrier-based delivery strategies for Alzheimer's and Parkinson's disease, with particular emphasis on their pharmacokinetic and pharmacodynamic performance. Collectively, the evidence indicates that nose-to-brain nanocarriers can effectively address key limitations of conventional therapies by enhancing brain targeting and therapeutic efficacy. However, successful clinical translation will require addressing formulation-related challenges such as mucociliary clearance, nasal irritation, burst drug release, and long-term safety, alongside well-designed clinical studies. Future research should therefore focus on exploring emerging delivery platforms to further advance nose-to-brain strategies for the management of neurodegenerative diseases.