PDRN

A mixture of DNA fragments extracted from salmonid fish sperm and studied as an adenosine A2A receptor agonist for wound healing, with prescription products in Italy and South Korea, no US approval, and no peptide structure.

Also referenced as: Polydeoxyribonucleotide, PDRN injection, Placentex, Placentex Integro, Rejuvenex, salmon DNA, sodium DNA, deoxyribonucleotide polymer

Also appears in: Dermal

COA Public product evidence No certificate records are bound to a tracked PDRN product page A record counts here only when a vendor publishes a certificate against one of its own tracked PDRN product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

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What is PDRN?

PDRN is not a peptide. Polydeoxyribonucleotide is a mixture of double-stranded DNA fragments, linear polymers of deoxyribonucleotides with molecular weights spread between roughly 50 and 1,500 kDa, extracted from the sperm of farmed salmonid fish — rainbow trout (Oncorhynchus mykiss, called “salmon trout” in the product literature) or chum salmon (O. keta) — and purified and sterilized at high temperature so that the fish proteins and peptides are denatured and removed (Squadrito et al., Frontiers in Pharmacology, 2017;8:224). It has no amino-acid sequence, no single molecular weight, and no defined active molecule; what a vial contains is a size distribution of DNA, with the Italian product averaging around 350 kDa. The compound was developed in Italy, where the first product, Placentex, was authorized in 1994 — the brand name recalls the human placenta from which PDRN was originally extracted before fish sperm became the commercial source (Marques et al., Biomolecules, 2025;15(1):148).

It reaches the research-peptide market from two directions. The first is clinical: PDRN is a prescription medicine in Italy and a registered pharmaceutical in South Korea, where it is injected into wounds, tendons, and joints, so it carries a genuine regulatory history that most research-market compounds lack. The second is cosmetic: the Korean “salmon DNA” skin-booster trend made PDRN and its longer-chain relative, polynucleotide (PN), familiar names in aesthetic medicine, and that demand spilled into research vendors’ catalogs as lyophilized powder and topical serums. In the United States no PDRN drug or device has been approved or cleared.

How it works

PDRN is proposed to act through two mechanisms, one receptor-mediated and one purely nutritional, and most of the mechanistic literature comes from two Italian groups.

• Adenosine A2A receptor agonism. In primary human skin fibroblasts, both PDRN and adenosine increased proliferation; the effect of PDRN was blocked by the A2 antagonist DMPX but not by the A1 antagonist DPCPX, was mimicked by an A2 agonist, and was accompanied by a DMPX-sensitive rise in cytosolic calcium. The authors concluded that PDRN acts partly through A2-subtype purinergic receptors and partly as a pro-drug that feeds the cells deoxyribonucleotides (Thellung et al., Life Sciences, 1999;64(18):1661–1674). The Messina group later attributed the receptor effect specifically to A2A, and that attribution is the basis for every subsequent “A2A agonist” description of the compound.
• Receptor dependence shown in animal disease models. In collagen-induced arthritis in mice, daily PDRN reduced clinical and histological arthritis, lowered cartilage and circulating HMGB-1, TNF-α, and IL-6, and raised IL-10; co-administering DMPX abolished the protection, which is the standard pharmacological test for a receptor-dependent effect (Bitto et al., Arthritis & Rheumatism, 2011;63(11):3364–3371). The same antagonist design showed that DMPX abolished PDRN’s effects on angiogenesis, VEGF, and wound-breaking strength in genetically diabetic mice (Galeano et al., Wound Repair and Regeneration, 2008;16(2):208–217); a follow-up study in the same model, without an antagonist arm, reported that PDRN restored cyclin/CDK expression and granulation-tissue proliferation during impaired healing (Altavilla et al., Surgery, 2011;149(2):253–261).
• The salvage pathway. Once injected, PDRN is degraded by nucleases into nucleosides and nucleotides that cells can take up and reuse for DNA synthesis. In hypoxic or damaged tissue, where de novo nucleotide synthesis is energetically limited, this supply is proposed to support proliferating cells independently of any receptor (Squadrito et al., Frontiers in Pharmacology, 2017).
• Why mechanism may not transfer between products. The 2017 review states that A2A binding “seems to be linked to DNA origin, molecular weight and manufacturing process,” which is a claim that the receptor pharmacology belongs to a specific manufactured product rather than to DNA fragments in general. The same authors note that defibrotide, another oligonucleotide mixture (porcine intestinal-mucosa DNA, FDA-approved for hepatic veno-occlusive disease), has a different size distribution and does not share PDRN’s wound-healing activity. A 2022 corrigendum to the review discloses that the first author received research support from Mastelli, the manufacturer, and that four of its authors are co-inventors on PDRN patents.

Research status

The evidence is uneven: one adequately sized blinded trial in wound healing, a cluster of small Korean musculoskeletal trials with active comparators, and an aesthetic literature that is mostly observational.

• Diabetic foot ulcers — the best trial. A randomized, double-blind, placebo-controlled trial at two Italian centers enrolled 216 patients with hard-to-heal Wagner grade 1–2 ulcers (110 PDRN, 106 placebo) treated for eight weeks by intramuscular and perilesional injection. Complete healing occurred in 37.3% of PDRN patients versus 18.9% on placebo (P = .0027; hazard ratio 2.20, 95% CI 1.29–3.75); median time to closure was 30 versus 49 days, and median re-epithelialized area 82.2% versus 49.3% (Squadrito et al., Journal of Clinical Endocrinology & Metabolism, 2014;99(5):E746–E753; registered as NCT00638872, University of Messina, phase 4). A 2015 corrigendum corrected the description of the administration route. The trial was run by the group that developed the mechanism story and used the Italian branded product; it has not been independently replicated at that scale.
• Other wound and epithelial trials. Smaller randomized, double-blind studies reported faster re-epithelialization of skin-graft donor sites with intramuscular plus subcutaneous PDRN in 26 patients (Rubegni et al., Current Medical Research and Opinion, 2001;17(2):128–131), faster corneal re-epithelialization after photorefractive keratectomy with PDRN eye drops in 60 eyes (Lazzarotto et al., European Journal of Ophthalmology, 2004;14(4):284–289), and smaller pressure ulcers in a 23-patient Korean trial of intramuscular and perilesional PDRN (Kim et al., Journal of Korean Medical Science, 2014;29 Suppl 3:S222–S227). A 2026 systematic review of PN and PDRN in regenerative dermatology, which searched through January 2026, found only seven randomized trials across skin rejuvenation, postoperative scar prevention, and wound healing, totaling 183 participants (a dermatologic scope that did not take in the 216-patient diabetic foot ulcer trial), and judged the wound-healing results the most consistent while calling the whole evidence base small and heterogeneous (Alhussain et al., Cureus, 2026;18(7):e112403).
• Knee osteoarthritis. A meta-analysis pooled five randomized trials (290 patients, 14 to 50 per trial) of intra-articular PDRN against hyaluronic acid. PDRN produced better pain scores at one and two months but not at four months, no difference in function (KOOS/KSS) at any time point, and no difference in adverse events; three of the five trials were rated at high risk of bias and the authors noted that no large trial exists (Kim et al., Medicine, 2019;98(39):e17386). The one Korean double-blind trial in that set assigned 30 evaluable patients to hyaluronic acid plus PDRN or hyaluronic acid alone and reported differences at six months with no treatment-emergent adverse events (Yoon et al., Annals of Rehabilitation Medicine, 2019;43(2):204–214). Every trial in this indication used hyaluronic acid as the comparator; no saline-controlled intra-articular trial has been published.
• Tendon and fascia. In chronic plantar fasciitis, 40 patients randomized to three weekly PDRN or saline injections showed a significant advantage for PDRN at 12 weeks but not at four weeks (Kim and Chung, International Orthopaedics, 2015;39(7):1329–1334); against corticosteroid in 44 patients, steroid relieved pain better at two and six weeks with no difference at six months (Lee et al., Foot & Ankle Surgery, 2020;26(6):657–661). A 2021 meta-analysis of PDRN for tendon or ligament pain could include only one randomized trial alongside three retrospective series (Gwak et al., Medicine, 2021;100(19):e25792), and a 2023 systematic review of tendon disorders found nine studies — seven clinical, two in vivo — covering 169 patients in total (Bizzoca et al., International Journal of Molecular Sciences, 2023;24(5):4582). A quadruple-blind Korean phase 4 trial of PDRN versus saline in rotator cuff tears (NCT03916198, n=79) was completed in February 2022 with no results posted to the registry, and a Korean trial of epidural PDRN for lumbar spinal stenosis (NCT04401735) is listed with unknown status.
• Terminated and stalled programs. The manufacturer’s own open-label phase 4 study of intramuscular Placentex in scleroderma (NCT03388255) was terminated in 2019 after enrolling 25 patients, citing recruitment difficulty in a rare condition; a separate explorative open cohort in localized scleroderma, also 25 patients, was published afterward (Romagnuolo et al., Biomedicines, 2023;11(4):1190). No PDRN program has reached a regulatory submission in the United States or the European Union’s centralized procedure.
• Current activity. As of October 2026 the registry shows investigator-initiated trials recruiting in Egypt (split-face PDRN versus non-cross-linked hyaluronic acid after subcision for rolling acne scars; PDRN versus saline alongside fractional CO₂ laser for facial scars), a Brazilian periocular-wrinkle study that has finished enrolling, a United Kingdom periodontal trial of a polynucleotide–hyaluronic acid device, and a Spanish dental clinic’s not-yet-recruiting periodontal study of the same device. Completed but unpublished-to-registry Korean trials cover postoperative scars and lateral epicondylitis, and a Mexican study used PDRN for vulvovaginal “biorevitalization.” No United States site appears in any PDRN record; the only US-sited study the intervention search returns is a defibrotide trial. There is no US trial of injectable PDRN and no sponsor-led development toward FDA approval.

Common dosage forms

In Italy, Placentex is a prescription medicine supplied as 5.625 mg/3 mL (Placentex Integro) and 2.25 mg/3 mL ampoules labeled for intramuscular or subcutaneous injection, a 0.08% cream, a 0.75 mg/3 mL cutaneous solution for soaking gauze, and 0.75 mg/mL eye drops. In South Korea, PDRN is regulated as a prescription pharmaceutical and sold as injection ampoules and prefilled syringes under several brands (Placentex Inj., Rejuvenex Inj., HiDr, Newdien, and others), alongside PDRN creams and eye drops, while the longer-chain polynucleotide (PN) skin boosters such as Rejuran are classed as medical devices and PDRN in topical cosmetics is declared as sodium DNA or hydrolyzed DNA (Kim, Pharmaceutics, 2025;17(8):1024).

Research vendors sell PDRN as lyophilized powder in vials labeled by milligram content and marked for research use, and as topical serums, creams, and “ampoule” cosmetics. Because the material is a size distribution of DNA rather than a molecule, labeled milligrams say nothing about the fragment-size profile, and some newer cosmetic supplies use microbially or plant-derived DNA rather than salmon sperm. No FDA-approved product exists, PDRN has not been placed on the FDA’s section 503A bulk drug substances list, and no licensed US compounding route exists.

Key considerations

• Not a peptide, and not a single compound. PDRN has no sequence and no defined molecular weight, so a certificate of analysis cannot confirm identity by mass the way it can for a synthetic peptide. Meaningful characterization is a molecular-weight distribution, nucleic-acid purity (A260/A280), residual protein, and endotoxin. The originating group’s own position is that A2A activity depends on DNA source, size, and manufacturing process, which means trial results obtained with the Italian pharmaceutical do not automatically describe any other product carrying the name.
• Regional approvals are real but do not change the US picture. Italy has authorized PDRN since 1994 and South Korea registers it as a pharmaceutical; those products are prescription injectables used for wounds and dystrophic connective-tissue conditions. In the United States there is no approved drug, no cleared device, no 503A listing, and no registered trial of injectable PDRN. Investigator-initiated trials are active abroad, but there is no sponsor-led path toward US approval. The Research Market status reflects regional prescription approvals with no US approval or development program aimed at US approval.
• The evidence is one good trial deep. The 216-patient diabetic foot ulcer trial is a properly blinded, placebo-controlled study with a meaningful endpoint, but it came from the group that owns the mechanism and the patents, used a single branded product, and has not been replicated. Everything else — knee osteoarthritis, tendinopathy, scars, wrinkles — rests on trials of 14 to 60 patients, usually against an active comparator and often unblinded, and the systematic reviews that pooled them all concluded that larger trials are needed.
• Safety data are reassuring but narrow. Published trials report no injection-related complications, and the Italian label’s only contraindication is hypersensitivity to the product. Manufacturers argue that high-temperature purification removes immunogenic fish proteins, but hypersensitivity in fish-allergic patients has not been formally studied. Intra-articular and epidural injection are not on the Italian label; a 2025 Korean review describes an approved knee-osteoarthritis indication for Korean PDRN injections, which could not be confirmed against the MFDS register. No US pharmacovigilance covers the product, and nothing in the trial literature addresses the long-term effects of repeated injection.
• Names collide in ways that matter. PDRN and PN are both salmon-sperm DNA and the terms are used interchangeably in marketing; there is no standardized size cutoff, and one 2025 proposal sets it at 1,500 kDa with PN above and PDRN below (Marques et al., Biomolecules, 2025). PN products are devices with a different regulatory basis and a structural, hydrogel-like rationale, so evidence for one is not evidence for the other. “Placentex” no longer contains placenta, and PDRN should not be confused with defibrotide, a different oligonucleotide mixture that is FDA-approved for an unrelated hematologic indication.