Preparation and characterization of polydeoxyribonucleotide-poly(L-lysine) nanospheres with high penetration and hydrating properties for skin applications.

Polydeoxyribonucleotide (PDRN) is a bioactive DNA-derived macromolecule that holds great potential in high-end cosmeceutical and biomedical applications. However, its high molecular weight and susceptibility to degradation severely limit its transdermal absorption and bioavailability. Poly(L-lysine) (PLL) is a cationic polypeptide capable of interacting with negatively charged biomacromolecules through its abundant amino groups, providing a physicochemical basis for the construction of PDRN-PLL complexes. In this study, PDRN-PLL nanospheres were successfully constructed using electrostatic co-assembly technology, and their physicochemical properties and biological functions were systematically characterized. Results demonstrated that the prepared nanospheres had a mean particle size of 138.0 ± 4.3 nm and a PDI of 0.40 ± 0.03, with a PDRN loading efficiency of 93.3%, while exhibiting good storage stability. Furthermore, the proposed nanospheres showed outstanding antioxidant activity and cytocompatibility, effectively promoting the skin penetration and retention of PDRN, with significantly enhanced moisturizing efficacy, thereby overcoming its inherent application limitations. These findings suggest that PDRN-PLL co-assembly may provide a feasible formulation approach for improving the transdermal delivery efficiency, skin retention capacity, and moisturizing performance of PDRN.