Review of preclinical nose-to-brain biodegradable nanocarriers (lipid-, polymer-, hybrid-based nanoparticles, gels, nanoemulsions, sprays) for Alzheimer’s and Parkinson’s therapies, emphasizing pharmacokinetic/pharmacodynamic gains and formulation challenges for clinical translation.

Highlights a translational delivery approach that could substantially boost brain bioavailability and reduce systemic toxicity for PD drugs, making it a useful roadmap for advancing therapies if key nasal formulation and clinical testing barriers are solved.

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. 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, 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, Polymer-based, hybrid nanoparticles, nasal gel-based systems, nanoemulsions, nanosuspensions, 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. This indicates that nose-to-brain nanocarriers can effectively address key limitations. However, successful clinical translation will require addressing formulation-related challenges such as mucociliary clearance, nasal irritation, burst drug release, alongside well-designed clinical studies. Future research should focus on exploring emerging delivery platforms to advance nose-to-brain strategies for the management of neurodegenerative diseases.