Polydeoxyribonucleotide-spermidine nanoparticles: Preparation, characterization, and verification of skin anti-aging efficacy

Abstract

Regenerative medicine, with stem cells and tissue engineering as its core, is dedicated to the regeneration of skin and organs and the treatment of diseases. Polydeoxyribonucleic acid (PDRN) has been demonstrated to promote skin regeneration and anti-aging in the field of regenerative medicine, yet its application is constrained by its inherent characteristics, including its high electronegativity, poor transdermal delivery, low transmembrane and susceptibility to degradation. Spermidine is a trivalent molecule with a variety of biological activities, including autophagy induction, cell regeneration and free radical scavenging. Herein, PDRN was innovatively coagulated into nanoparticles with spermidine to construct nucleic acid delivery vehicles (PDRN-NPs), and the preparation process was optimized and characterized in multiple dimensions, resulting in homogeneous PDRN-NPs with an average particle size of 201.9 ± 5.3 nm, which were able to be enriched in the periphery of fibroblasts, and the phagocytosis capacity of macrophages was significantly increased by 96 % and the expression of cellular mitochondrial ATP was increased by 46.14 %. PDRN-NPs have been demonstrated to potently inhibit the expression of TNF-α, IL-6 and MMP-1, while concomitantly promoting the expression of the NRG1 protein. Furthermore, PDRN-NPs have been shown to enhance cell migration by 25.63 %, increased in vitro percutaneous permeability by 202.3 % and in vivo permeability by 143.4 %. Concurrently, the human efficacy evaluation demonstrated that PDRN-NPs could enhance the structure and function of the skin from multiple levels, exhibiting specific anti-skin aging efficacy. This study provides a theoretical and experimental basis for the application of nucleic acid drug delivery and cosmetics, and promote the development of regenerative medicine fields.