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RESEARCH PAPER ANALYSIS

Nanomedicines for neurodegenerative ageing: nasal delivery innovations for Alzheimer's and Parkinson's disease.

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.

PMID41989792
JournalJournal of drug targeting
Publication Date2026-04-27
Ingested2026-04-28 08:58 PM
EXECUTIVE SUMMARY

What the AI sees

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.

WHY IT MATTERS

Research significance

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.

ABSTRACT

Source abstract

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.

SUPPORTING PAPER SET

32 more papers to review

Ranked by current scoring engine
1 The cGAS-STING-Glymphatic-gut Axis in Parkinson's disease: A proposed self-amplifying triad of Neuroinflammation and therapeutic opportunity. International immunopharmacology 91.0 2 Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications. Cells 91.0 3 Flavonoids improve neurotransmitters for Parkinson's treatment: mechanism and therapeutic potential. Frontiers in pharmacology 88.0 4 Alpha-Lipoic Acid and Biotin in Neurodegenerative Diseases: Convergent Mechanistic Insights from Preclinical Models to Clinical Perspectives. Neurology international 78.0 5 The Gut Microbiota in Parkinson's Disease: Mechanistic Insights into Microbial-Host Interactions. Microorganisms 85.0 6 Linking inflammation, metabolic dysfunction, and neurodegeneration: a comprehensive review of TLR2 pathways in type 2 diabetes. Frontiers in clinical diabetes and healthcare 80.0 7 Neuroprotective effects of GLP-2 and a GLP-2/GIP dual receptor agonist in an MPTP-induced mouse model of Parkinson's disease. Peptides 86.0 8 TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation. Nature communications 91.5 9 Lipid Metabolism and Neurodegeneration: Mechanistic Insights and Therapeutic Targets. Ageing research reviews 82.0 10 Shared functional microbiome signatures in Parkinson's disease and constipation predominate irritable bowel syndrome despite taxonomic divergence. Brain, behavior, & immunity - health 80.0 11 Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases. ChemMedChem 74.0 12 Biomimicking neuromelanin reverses the gait deficits and dopaminergic neuronal loss in the Parkinson's disease. Colloids and surfaces. B, Biointerfaces 86.0 13 Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. Experimental physiology 84.0 14 Flavonoid Rutin Reduces Intestinal Inflammation in an Experimental Model of Parkinson's Disease. Neurotoxicity research 70.0 15 Nanostructured Lipid Carriers Enhance Brain Delivery and Antioxidant Efficacy of a Small-Molecule MAO B Inhibitor for Neurodegenerative Disease Therapy. Molecular pharmaceutics 78.0 16 Pathophysiological Role of the Gut Brain Axis in Parkinson's Disease: From Microbial Metabolites and Intestinal Permeability to Central Neuroinflammation. Current neurovascular research 86.0 17 Parkinson's Disease: From Metabolism to Genetics-A Comprehensive Review. Current issues in molecular biology 86.0 18 Navigating the cholesterol maze: Key insights on use of statins in neurodegenerative disorders. Neuroprotection (Chichester, England) 76.0 19 Integrative network pharmacology delineates dual GPCR and non-GPCR mechanisms of blended and individual Taikong Blue lavender and Pingyin rose essential oils in neurodegenerative and psychiatric disorders. Computers in biology and medicine 65.0 20 Models of neuroprotection in Parkinson's disease: Exploring cellular, molecular, and microenvironmental targets. Experimental neurology 78.0 21 Hyaluronic acid: emerging roles and biomaterial innovations in Alzheimer's and Parkinson's disease therapy. Frontiers in pharmacology 75.2 22 Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy. Frontiers in pharmacology 75.0 23 Lipid droplets in neurodegenerative diseases: pathological drivers and therapeutic vulnerabilities. Cell death discovery 82.0 24 Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions. Frontiers in microbiology 74.0 25 Long non-coding RNAs in neurodegenerative diseases - Molecular mechanisms, liquid biopsy biomarkers, and therapeutic targets: A review. Biomolecules & biomedicine 84.0 26 Neurosyphilis and Parkinsonism: Overlapping Pathophysiology and Emerging Therapeutic Insights. Current neurovascular research 76.0 27 Molecular biochemistry of soluble epoxide hydrolase in lipid mediator pathways and neuroinflammatory responses. The Journal of steroid biochemistry and molecular biology 82.0 28 Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential. Cell stress 83.3 29 Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease. Central nervous system agents in medicinal chemistry 64.0 30 Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder. Signal transduction and targeted therapy 84.0 31 HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches. Inflammopharmacology 78.0 32 Beyond acid-base dyshomeostasis: Dynamic instability of neuronal lysosomal pH as a pathogenic mechanism and therapeutic target in neurological diseases. Biochemical pharmacology 88.0
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