Plasma-Engineered PDRN: Surface Charge Neutralization and Nanosizing Enhance Uptake and Regeneration Potential

<b>Background</b>: Polydeoxyribonucleotide (PDRN) is increasingly used in dermatology and cosmetic applications owing to its regenerative and anti-aging properties. However, its topical use is limited by its high molecular weight and anionic charge, which restrict skin penetration. <b>Methods</b>: In this study, we employed a nitrogen-oxygen plasma treatment to PDRN to overcome these limitations and characterized its physicochemical properties and in vitro efficiency. <b>Results</b>: Upon plasma treatment, PDRN's surface charge was attenuated and its hydrodynamic size decreased, leading to improved uptake and markedly increased cell migration activity. <b>Conclusions</b>: These findings suggest that plasma treatment can transform PDRN into a cosmetically viable active ingredient and may provide a general strategy for adapting other high-molecular-weight bioactives for topical delivery.