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Original Research | Open Access

Liposome-based loading enhances the distribution of nicotinamide riboside chloride into the brain and its neuroprotective effects in cerebral ischemic mice

Xinxin Xiea,1, Qianqian Konga,1, Yan Chenb, Zhongzheng Yangc, Zeqiang Wuc, Yue Xiaoc, Yajun Chend, Zhiyuan Yua,e, Xiang Luoa,e, Wensheng Qua,e()
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Department of Pharmacology, Tongji Medical University, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
Wuhan Biobank, Human Genetic Resource Bank, Wuhan 430030, Hubei, China
Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430030, Hubei, China
Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China

1 These authors contributed equally to this work.

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Abstract

Objective

Nicotinamide riboside (NR) is neuroprotective; however, its low permeability through the blood‒brain barrier restricts its therapeutic efficacy in central nervous system diseases. Compared with oral NR administration, liposome-based NR loading is hypothesized to improve its pharmacological properties during cerebral ischemia, especially when administered intravenously.

Methods

NR chloride (NRC) was encapsulated in an optimized liposome composition and administered by bolus intravenous injection. This was followed by examination of its pharmacokinetics, organ distribution, and effects on cerebral ischemia in mice.

Results

Compared with conventional NRC solution, the liposome form led to a 2.76-fold higher Cmax and a 5.32-fold higher AUC0–24h in plasma after a bolus injection of 40 mg/kg. In healthy mouse brain, it caused a significant elevation of Cmax (2.93-fold) and AUC0.25–24h (2.68-fold). In cerebral ischemia model mice, NRC liposomes increased the drug concentration at 1 and 6 h post-ischemia, increased tissue NAD+ and ATP levels, reduced infarct volume (by a further decrease of 35.4%), ensured neuronal survival, attenuated glial activation, and significantly improved behavioral recovery compared with conventional NRC treatment.

Conclusion

Liposome loading enhances the brain distribution and therapeutic effects of NRC, which strengthens its possibility for clinical translation and neurorestoration in stroke.

Keywords

Cerebral ischemiaNicotinamide ribosideLiposomeNicotinamide adenine dinucleotidePharmacokineticsNeuroprotection

Electronic Supplementary Material

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Journal of Neurorestoratology
Volume 12 Issue 2,
June 2024
Article number: 100111
DOI: 10.1016/j.jnrt.2024.100111
Cite this article:
Xie X, Kong Q, Chen Y, et al. Liposome-based loading enhances the distribution of nicotinamide riboside chloride into the brain and its neuroprotective effects in cerebral ischemic mice. Journal of Neurorestoratology, 2024, 12(2): 100111. https://doi.org/10.1016/j.jnrt.2024.100111
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