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Dual-Targeting Protein-Based Delivery System for Enhanced Drug Therapy of Neurodegenerative Disorders
Jia-Lin Wang1, Yi-Ying Dong1, Pei-Ling Liu1
1Key Laboratory of Biotechnology of Chinese Traditional Medicine of Hubei Province, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, School of Health Science and Engineering, Hubei University, Wuhan 430062, China.
ACS Applied Bio Materials
|May 12, 2025
Summary
This study presents a novel dual-brain targeting drug delivery system for Alzheimer's disease (AD). The system enhances drug penetration across the blood-brain barrier (BBB) and improves therapeutic outcomes for neurodegenerative diseases.
Area of Science:
- Nanotechnology and Drug Delivery
- Neuroscience and Neurodegenerative Diseases
Background:
- Conventional Alzheimer's disease (AD) treatments face challenges with low bioavailability due to the blood-brain barrier (BBB).
- Effective drug delivery across the BBB is crucial for treating central nervous system (CNS) disorders.
Purpose of the Study:
- To develop a dual-brain targeting, nose-to-brain drug delivery system for enhanced Alzheimer's disease treatment.
- To improve the blood-brain barrier (BBB) penetration and neuronal uptake of Donepezil.
Main Methods:
- Preparation of Donepezil-loaded nanoparticles (Donepezil@Tf/cRGD-CS) using a self-assembly method.
- Encapsulation of Donepezil within transferrin (Tf) nanoparticles decorated with cRGD-conjugated chitosan (cRGD-CS).
- Evaluation of BBB penetration using an in vitro BBB model and assessment of therapeutic effects.
Main Results:
- The dual-targeted nanoparticles demonstrated enhanced permeability across the in vitro BBB model.
- Donepezil@Tf/cRGD-CS showed improved cellular uptake by brain neurons.
- Significant reduction in Aβ25-35-induced neurotoxicity, apoptosis-related proteins, and Tau proteins compared to free Donepezil.
Conclusions:
- The developed dual-brain targeting system effectively enhances drug delivery across the BBB for Alzheimer's disease.
- This strategy offers a promising approach for improving therapeutic outcomes in CNS diseases.
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