Hydroxyapatite-based nano-drug delivery system for nicotinamide mononucleotide (NMN): significantly enhancing NMN bioavailability and replenishing in vivo nicotinamide adenine dinucleotide (NAD+) levels

Abstract

Abstract Objectives This study addresses the bioavailability challenges associated with oral nicotinamide mononucleotide (NMN) administration by introducing an innovative NMN formulation incorporated with hydroxyapatite (NMN–HAP). Methods The NMN–HAP was developed using a wet chemical precipitation and physical adsorption method. To assess its superiority over conventional free NMN, we examined NMN, nicotinamide adenine dinucleotide (NAD+), and nicotinamide riboside (NR) levels in mouse plasma and tissues following oral administration of NMN–HAP. Key findings NMN–HAP nanoparticles demonstrated a rod-shaped morphology, with an average size of ~50 nm, along with encapsulation efficiency and drug loading capacity exceeding 40%. In vitro, drug release results indicated that NMN–HAP exhibited significantly lower release compared with free NMN. In vivo studies showed that NMN–HAP extended circulation time, improved bioavailability compared with free NMN, and elevated plasma levels of NMN, NAD+, and NR. Moreover, NMN–HAP administration displayed tissue-specific distribution with a substantial accumulation of NMN, NAD+, and NR in the brain and liver. Conclusion NMN–HAP represents an ideal formulation for enhancing NMN bioavailability, enabling tissue-specific delivery, and ultimately elevating in vivo NAD+ levels. Considering HAP’s biocompatible nature and versatile characteristics, we anticipate that this system has significant potential for various future applications.