Topical PDRN-850K improves periocular wrinkles and dermal density two-fold over retinol in photodamaged skin.

Chronic ultraviolet (UV) exposure is a primary driver of photoaged skin, leading to dysfunctional dermal fibroblasts and disrupted extracellular matrix (ECM) homeostasis. While injectable polydeoxyribonucleotide (PDRN) has demonstrated regenerative effects, its mechanism and efficacy for topical delivery in photodamaged skin remain underexplored. Current anti-aging interventions often fall short in directly restoring the dermal microenvironment, highlighting a need for approaches that promote biological structural repair rather than just symptomatic correction. This study investigates a medium-length PDRN formulation to address this gap.

Researchers investigated PDRN-850K's mechanism, delivery, and efficacy across multiple models. Pathway activation was assessed in basal human dermal fibroblasts using western blotting, gene expression analysis, and pharmacological inhibition. Skin delivery was evaluated via confocal Raman spectroscopy in a reconstructed epidermal model, complemented by ex vivo (FITC-labeled porcine skin) and pilot in vivo human penetration studies. Tissue-level effects were examined in a UV-irradiated human ex vivo skin model. Clinical efficacy was determined in a randomized, double-blind, split-face study comparing 0.1% PDRN-850K eye cream with 0.1% retinol over 28 days.

In basal fibroblasts, PDRN-850K activated PI3K-Akt, TGF-β/Smad, and autophagy-related signaling pathways, with pharmacological inhibition of these pathways reducing ECM gene induction. Raman analysis confirmed time-dependent distribution of PDRN-associated signals into viable epidermal regions, supported by ex vivo porcine skin and pilot in vivo human studies. In UV-irradiated ex vivo human skin, PDRN-850K significantly increased viable epidermal thickness and upregulated multiple collagens, elastic fiber-associated proteins, and YAP. The clinical trial demonstrated superior results for the PDRN formulation:

Clinically, PDRN-850K achieved approximately two-fold greater improvements in periocular wrinkles, dermal thickness, density, and eye bag parameters compared with retinol, with good tolerability. These findings collectively support PDRN-850K as a potent topical agent for repairing photodamaged skin.