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Intranasal Administration of CNS Therapeutics to Awake Mice
Published on: April 8, 2013
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Intranasal triptolide in mice: a strategy to reduce neuroinflammation and boost cognitive function.
Min Yan1, Lan Zhang2, Junwei Zhao3
1Academy of Chinese Medicine Sciences, Henan University of Chinese Medicine, Zhengzhou, China.
Immunopharmacology and Immunotoxicology
|December 29, 2025
Summary
Intranasal triptolide-loaded liposomes (TPL) enhance brain delivery and reduce toxicity for treating neuroinflammation and Alzheimer's disease (AD). This novel TPL system shows significant therapeutic potential for neurodegenerative disorders.
Area of Science:
- Pharmacology and Drug Delivery
- Neuroscience
- Biomedical Engineering
Background:
- Triptolide (TP) exhibits therapeutic potential but suffers from high systemic toxicity.
- Neurodegenerative diseases like Alzheimer's disease (AD) and neuroinflammation require effective brain-targeted therapies.
- Liposomal drug delivery systems offer a promising strategy to improve drug bioavailability and reduce side effects.
Purpose of the Study:
- To develop triptolide-loaded liposomes (TPL) for intranasal delivery.
- To evaluate the brain targeting, safety, and therapeutic efficacy of intranasal TPL in neuroinflammatory and AD models.
- To elucidate the underlying mechanisms of TPL's therapeutic effects.
Main Methods:
- Liposomes encapsulating triptolide (TPL) were prepared using thin-film hydration.
- Biodistribution of liposomes via nasal, oral, and intravenous routes was assessed using *in vivo* imaging.
- Safety and efficacy of intranasal TPL were evaluated in LPS-induced neuroinflammation and APP/PS1 AD mouse models, including behavioral, histopathological, and molecular analyses.
Main Results:
- Nasal administration resulted in superior brain accumulation of liposomes compared to other routes.
- Optimized TPL demonstrated favorable characteristics including high encapsulation efficiency and sustained release.
- Intranasal TPL exhibited reduced systemic toxicity, improved cognitive and behavioral performance, attenuated neuroinflammation, reduced amyloid-beta plaques, and modulated apoptosis and survival pathways in disease models.
Conclusions:
- Intranasal TPL is an effective strategy for enhancing brain delivery of triptolide while minimizing systemic exposure.
- The TPL system demonstrates multimodal therapeutic benefits, including anti-inflammatory, anti-amyloid, and pro-survival effects.
- Nasal TPL holds significant therapeutic promise for treating neurodegenerative disorders like Alzheimer's disease.
