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Recent Advances in Donepezil Delivery Systems via the Nose-to-Brain Pathway
Jiyoon Jon1, Jieun Jeong1, Joohee Jung1
1College of Pharmacy, Duksung Women's University, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of Korea.
Pharmaceutics
|August 28, 2025
Summary
Nose-to-brain delivery of Donepezil (DPZ) offers improved Alzheimer's disease (AD) treatment by bypassing the blood-brain barrier. Intranasal administration significantly enhances brain drug concentration and therapeutic efficacy with low toxicity.
Area of Science:
- Neuroscience
- Pharmacology
- Drug Delivery Systems
Background:
- Donepezil (DPZ) is an acetylcholinesterase (AChE) inhibitor used for Alzheimer's disease (AD).
- Oral DPZ formulations exhibit limited bioavailability due to poor blood-brain barrier (BBB) permeability.
- Novel drug delivery systems are needed to enhance direct brain targeting of DPZ.
Purpose of the Study:
- To review and analyze nose-to-brain (N2B) delivery systems for Donepezil (DPZ).
- To evaluate the efficacy and safety of intranasal (IN) DPZ formulations for Alzheimer's disease (AD).
- To discuss advancements in N2B technologies for enhanced brain drug delivery.
Main Methods:
- Systematic review of N2B research for DPZ formulations.
- Analysis of various IN delivery systems: lipid-based, solid particle-based, solution-based, gel-based, and film-based.
- Evaluation of in vivo data on brain drug concentration and direct delivery ratio.
Main Results:
- Intranasal (IN) administration achieved more than double the brain drug concentration compared to other routes within 15 minutes.
- The N2B system demonstrated a direct delivery ratio of 80.32%.
- Developed DPZ formulations showed low toxicity and high therapeutic efficacy for AD.
Conclusions:
- Nose-to-brain (N2B) delivery is a highly promising approach for enhanced Alzheimer's disease (AD) treatment.
- Intranasal (IN) administration of DPZ bypasses the BBB, improving bioavailability and CNS targeting.
- Optimized N2B formulations enhance mucosal residence time and therapeutic outcomes for AD.
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