Nanoformulated PDRN Improves Anti‐Inflammatory and Wound Healing Activities

Polydeoxyribonucleotide (PDRN), a bioactive DNA fragment, has been known to promote anti-inflammatory responses and wound healing primarily via adenosine A₂A receptor activation. However, low molecular weight PDRN can undergo rapid degradation, limiting its sustained therapeutic efficacy. In this study, we developed a scalable method to produce high-purity, and low molecular weight PDRN (c.a. 325 bp) from calf thymus DNA via physical fragmentation. To enhance its stability and delivery, PDRN was encapsulated in poly(lactic-co-glycolic acid) (PLGA) to form PDRN/PLGA nanoparticles, yielding uniform and spherical particles (336 ± 43 nm). These nanoparticles exhibited excellent colloidal stability and biodegradability (38.3% over 14 days), with sustained PDRN release (88.39% over 14 days). Moreover, the nanoformulation effectively protected PDRN from thermal, acidic, enzymatic, and UV degradation. The PDRN/PLGA nanoparticles, which exhibited no cytotoxicity or hemolysis, demonstrated superior anti-inflammatory and wound-healing efficacy compared to free PDRN. In an in vitro lipopolysaccharide (LPS)-induced inflammatory wound model, they significantly accelerated wound closure compared to both LPS-treated and untreated controls. These results suggest that nanoformulation effectively protects low molecular weight PDRN, thereby significantly enhancing its therapeutic activity and underscore the potential of PDRN/PLGA nanoparticles as a stable and effective platform for the regeneration of skin inflammation.