What question did this study set out to answer?

This research aims to develop an effective nasal delivery system for taxifolin to treat Alzheimer's disease by improving brain bioavailability.

February 8, 2026Open Access

A Nose-to-Brain Delivery System for Taxifolin Ameliorates Alzheimer’s Disease via Synergistic Attenuation of Oxidative Stress and Mitochondrial Dysfunction

MZMiao ZhangShandong University of Technology YWYusu WangJilin Agricultural University LZLiangliang ZhuJilin Agricultural University

Key Points

This research aims to develop an effective nasal delivery system for taxifolin to treat Alzheimer's disease by improving brain bioavailability.
Developed taxifolin-loaded thermosensitive hydrogel (TF-Gel) for intranasal administration.
Evaluated structural stability and functional performance of TF-Gel.
Assessed the effects of TF-Gel on mitochondrial function and oxidative stress markers in neuronal cells.
TF-Gel improves brain delivery and tissue penetration via intranasal administration.
It regulates mitochondrial dysfunction and reverses abnormal ATP, ROS, and MDA levels.
TF-Gel effectively enhances mitochondrial energy metabolism and reduces oxidative stress damage.

Abstract

The blood–brain barrier (BBB) presents the principal obstacle to drug delivery for Alzheimer’s disease (AD), severely restricting brain bioavailability and therapeutic efficacy. Taxifolin (TF) is a potent natural antioxidant with significant therapeutic potential. To enhance its efficacy in treating AD, we developed a brain-targeted delivery system based on a taxifolin-loaded thermosensitive hydrogel (TF-Gel). This platform integrates TF with a poly(N-isopropylacrylamide)-based thermosensitive hydrogel to enhance brain delivery, tissue penetration, and intracerebral retention via intranasal administration. TF-Gel exhibits excellent structural stability and functional performance, enabling efficient bypass of the BBB through the nasal–brain pathway. Furthermore, it regulates mitochondrial dysfunction, reverses abnormal levels of adenosine triphosphate (ATP), reactive oxygen species (ROS), and malondialdehyde (MDA) in neuronal mitochondria, repairs mitochondrial energy metabolism, restores mitochondrial dynamic balance, improves oxidative stress damage, and blocks cell apoptosis pathways. Collectively, these results highlight the strong potential of the TF-Gel nasal delivery system as a mitochondria-targeted therapeutic strategy for AD.

AI से पूछें

Bookmark

View Full Paper