Elastic cationic liposomal nanogels: a novel platform for topical nicotinamide mononucleotide delivery

Nicotinamide mononucleotide (NMN), a potent nicotinamide adenine dinucleotide (NAD⁺) precursor, has demonstrated significant potential in mitigating mitochondrial oxidative stress, alleviating degenerative diseases, and reducing reactive oxygen species (ROS) generation. However, its topical application is hindered by inherent challenges, including high hydrophilicity, poor skin permeability, and limited stability. To address these limitations, we developed elastic cationic liposomal nanogels (EC-Lip-nanogels), a novel delivery system composed of Nap-FF-GHK nanogels and elastic cationic liposomes (EC-Lips). Nap-FF-GHK peptide was synthesized by coupling the self-assembled scaffold Nap-FF with the anti-aging module GHK, which would be self-assembled into cationic nanogels. EC-Lips was constructed by incorporating edge activators (EAs) into cationic liposomes (C-Lips). The NMN-loaded EC-Lip-nanogels were systematically characterized, demonstrating favorable physicochemical properties with an average particle size of 53.2 nm, a zeta potential of +14.0 mV, and a high encapsulation efficiency of 90.2%. Notably, the penetration enhancement achieved by EC-Lips and EC-Lip-nanogels was 22.7% and 16.0%, respectively, compared to free NMN. This study might establish EC-Lip-nanogels as a promising platform for improving the skin permeability of NMN and other hydrophilic bioactive molecules, offering a transformative approach for topical applications.