A Liposomal Formulation Enhances the Anti-Senescence Properties of Nicotinamide Adenine-Dinucleotide (NAD⁺) in Endothelial Cells and Keratinocytes

Nicotinamide adenine-dinucleotide (NAD⁺) supplementation is a promising strategy to delay cellular aging in different areas, including cosmetic dermatology. However, low bioavailability and stability of NAD⁺ formulations are the main factors limiting its effectiveness as an anti-aging treatment. In light of the above, a liposomal formulation of NAD⁺ (LF-NAD⁺) was tested in this study and compared to NAD⁺ alone in primary human aortic endothelial cells (HAECs) and primary human epidermal keratinocytes (HEKas). Intracellular NAD⁺ was measured using a colorimetric assay. Cell survival was derived from lactate dehydrogenase release in supernatants. Cell senescence was measured by senescence-associated β-galactosidase staining. Molecular mechanisms underlying the reported effects were analyzed by Western blot. Skin penetration of NAD⁺ was measured ex vivo in skin explants, using infrared spectroscopy. Compared to control NAD⁺ alone, the LF-NAD⁺ formulation increased the intracellular NAD⁺ content and cell survival in HAECs, but not in HEKas. Instead, a significant reduction in the number of senescent cells was observed in both HAECs and HEKas. LF-NAD⁺ treatment was associated with a reduced expression of p16 in both HAECs and HEKas, and to a significant reduction in p21 in HEKas alone. Finally, LF-NAD⁺ increases the skin penetration of the active substance NAD⁺ by 30% compared to the application of NAD⁺ alone. LF-NAD⁺, enhances the anti-aging effects of NAD⁺ on vascular and skin cells. Such in vitro findings might indicate a potential anti-aging role in the microcirculation and in the epidermidis.