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

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 C_max and a 5.32-fold higher AUC_0–24h in plasma after a bolus injection of 40 mg/kg. In healthy mouse brain, it caused a significant elevation of C_max (2.93-fold) and AUC_0.25–24h (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.