Intranasal Delivery of siRNA Medications for Alzheimer’s Disease

Abstract

This presentation examines the developing strategy of delivering siRNA therapeutics intranasally as an innovative method for addressing Alzheimer’s disease. It starts with background details on Alzheimer’s pathology, emphasizing the difficulties presented by the blood–brain barrier (BBB) in traditional drug delivery. The discussion subsequently presents the nose-to-brain pathway, detailing how olfactory and trigeminal routes provide direct access to the brain, avoiding systemic circulation.

The process of siRNA therapy is explained, emphasizing gene silencing of targets like BACE1 (β-secretase) and APP (amyloid precursor protein), which play key roles in the production of amyloid-β. The ongoing research advancements are examined, encompassing the progression of delivery mechanisms from unprotected siRNA to sophisticated carriers like lipid nanoparticles, PLGA nanoparticles, and modified stem cell exosomes.

Research examples, including RVG29-modified exosomes combined with BACE1 siRNA and berberine, show encouraging preclinical results in Alzheimer’s mouse models, featuring decreased amyloid accumulation, enhanced cognitive function, and robust safety profiles. The presentation emphasizes nanoparticle carriers and device design as essential elements for effective intranasal delivery, focusing on stability, mucosal adhesion, deposition efficiency, and user comfort.

Ultimately, future directions are addressed, focusing on AI-supported therapy design, biomarker identification, custom dosing, and translational forecasting models to enhance clinical implementation. In summary, this study frames intranasal siRNA delivery as a precise, non-invasive, and novel therapeutic approach, possessing significant promise to address existing challenges in Alzheimer’s therapy.

Authors

Wan Kiu Winkey CHENG - City University of Hong Kong, Department of Biomedical Engineering
Yiqing YANG - Co-author
Wing Hei CHOI - Co-author

Publication Details

Published: November 24, 2025
Publication Type: Review / Presentation
Publisher: Zenodo
DOI: 10.5281/zenodo.17702255
License: Creative Commons Attribution 4.0 International
Language: English
Keywords: Alzheimer Disease, Administration Intranasal, Biomedical Engineering, Medical Engineering

Citation

```bibtex @article{https://doi.org/10.5281/zenodo.17702255, doi = {10.5281/ZENODO.17702255}, url = {https://zenodo.org/doi/10.5281/zenodo.17702255}, author = {CHENG, Wan Kiu Winkey and YANG, Yiqing and CHOI, Wing Hei}, keywords = {Alzheimer Disease, Administration, Intranasal, Biomedical Engineering, FOS: Medical engineering}, language = {en}, title = {Intranasal Delivery of siRNA medications for Alzheimer’s Disease}, publisher = {Zenodo}, year = {2025}, copyright = {Creative Commons Attribution 4.0 International} }

Recommended citation: CHENG, Wan Kiu Winkey, YANG, Yiqing, & CHOI, Wing Hei. (2025). "Intranasal Delivery of siRNA medications for Alzheimer Disease." Zenodo. https://doi.org/10.5281/zenodo.17702255
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