Nicotinamide mononucleotide (NMN), a precursor to the essential coenzyme NAD+, is gaining attention for its potential anti-aging effects, particularly in the brain. However, NMN’s effectiveness is often limited by its rapid metabolism in the liver and low bioavailability, as well as by the blood-brain barrier (BBB), which restricts its access to the brain. Addressing these limitations, a new study developed a biocompatible polydopamine (PDA) platform to enhance the targeted delivery of NMN directly to the brain.

In this approach, the research team created a PDA-based delivery system with lactoferrin (Lf) ligands covalently attached to PDA spheres, resulting in the PDA-Lf-NMN platform. This modification improved the system’s ability to penetrate the BBB and increased NMN utilization within the brain. In trials with both young (3 months) and older (21 months) mice, PDA-Lf-NMN significantly elevated NAD+ levels in the brain compared to NMN alone. Notably, older mice treated with a low dose of PDA-Lf-NMN (8 mg/kg/day) showed improved spatial cognition.

Importantly, the nanomedicine was well-tolerated, with no signs of cellular necrosis or apoptosis, highlighting its safety and compatibility. This PDA-Lf-NMN platform offers a promising path for NMN delivery to the brain, potentially enhancing NAD+ levels to support longevity and address age-related brain conditions. Such targeted delivery systems could revolutionize treatments for brain aging and cognitive decline, providing new avenues for promoting brain health and resilience against aging.