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Microfluidics-Assisted Selective Depolarization of Axonal Mitochondria

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Published on: August 4, 2022

Three-stage sequential targeted nasal drops for correcting abnormal mitochondrial division in microglia.

Miaomiao Fei¹, Qidong Liu¹, Hui Zhang¹

¹Department of Anesthesiology and Perioperative Medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, PR China.

Bioactive Materials

|July 18, 2025

Summary

A novel nasal delivery system targets brain microglia to treat central nervous system (CNS) diseases by regulating mitochondrial division. This approach successfully delivered drugs and improved cognitive function in mouse models.

Keywords:

Abnormal mitochondrial division CNS diseases Hydrogel microspheres Microglia Nasal drops

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Published on: May 30, 2025

Area of Science:

Neuroscience
Biotechnology
Pharmacology

Background:

Abnormal mitochondrial division in microglia is implicated in central nervous system (CNS) diseases.
Challenges in treating CNS diseases include drug delivery to the brain, microglial targeting, and mitochondrial regulation.

Purpose of the Study:

To develop a novel three-stage sequential targeted nasal drops delivery system for noninvasive treatment of CNS diseases.
To achieve precise drug delivery to brain lesions, target microglia, and regulate mitochondrial function.

Main Methods:

Selection of dehydroepiandrosterone (DHEA) as a key neurosteroid regulating mitochondrial fission.
Development of surface-positively charged hydrogel microspheres for nasal mucosa targeting.
Construction of targeted liposomes carrying cytotoxic T lymphocyte-associated protein-4, modified into microspheres for microglial CD80/86 receptor binding.
In situ release of DHEA to regulate dynamin-related protein 1, inhibiting abnormal mitochondrial division and microglial activation.

Main Results:

The three-stage sequential nasal drops efficiently traversed the nose-to-brain pathway in murine and porcine models.
The system successfully targeted activated microglia via CD80/86 receptors.
Treatment significantly ameliorated anesthesia/surgery-induced cognitive dysfunction in mice.
Mitochondrial morphology and function were stabilized, and microglial activation was inhibited.

Conclusions:

The developed three-stage sequential nasal drip system is a promising noninvasive strategy for treating CNS diseases.
This method offers precise drug delivery, effective microglial targeting, and mitochondrial regulation.
The system demonstrates potential for therapeutic intervention in neurological disorders.