Clinical education article · Updated March 2026 · 9 min read · For licensed medical aesthetics practitioners
Polynucleotides (PN) and polydeoxynucleotides (PDRN) have become two of the most clinically discussed molecules in regenerative aesthetic medicine. Despite sharing the same chemical backbone — a linear polymer of deoxyribonucleotides linked by phosphodiester bonds — they differ in molecular weight, kinetics and dominant downstream effects[1]. In clinical practice, these differences translate into distinct indications, protocols and product choices.This article provides a structured overview of PN vs PDRN for aesthetic medicine practitioners: from molecular biology to injection protocols and evidence-based product selection. Internal links point directly to products available at Fräya Med Supply.
Quick answer: PN (polynucleotides) have a molecular weight ≥ 1500 kDa and primarily drive ECM remodelling and long-term structural regeneration. PDRN (polydeoxynucleotides) have a MW < 1500 kDa, showing faster A2A receptor activation and stronger anti-inflammatory effects. Both are used in aesthetic biostimulation protocols, often sequentially or in combination.
What Are Polynucleotides (PN)?
Polynucleotides (PN) are long-chain deoxyribonucleotide polymers with a molecular weight ≥ 1500 kDa, extracted primarily from fish gonads (trout, salmon). Their high molecular weight confers greater viscoelasticity and allows them to form a three-dimensional porous scaffold within the dermis, supporting extracellular matrix (ECM) remodelling over time.[1]
In injectable aesthetics, PN-based products are classified as medical devices (CE/MDR) and positioned as biostimulators targeting skin quality: density, elasticity, hydration and structural regeneration
What Is PDRN?
PDRN (polydeoxynucleotides) refers to shorter-chain fragments with a molecular weight < 1500 kDa, typically extracted from salmon sperm cells (Oncorhynchus keta, O. mykiss). The lower molecular weight results in faster diffusion, higher affinity for the adenosine A2A receptor, and a more pronounced anti-inflammatory and tissue-healing profile.[2]
The nomenclature distinction between PN and PDRN was formally proposed in 2025 (Marques et al.), establishing molecular weight as the primary differentiating criterion.[3]
PN vs PDRN: Key Clinical Differences
The table below summarises the clinically relevant differences. Note that both PN and PDRN activate the adenosine A2A receptor — the primary distinction lies in kinetics and downstream emphasis, not in a fundamentally different mechanism.[2][4]
| Feature | Polynucleotides (PN) | PDRN |
|---|---|---|
| Molecular weight | ≥ 1500 kDa | < 1500 kDa |
| Primary receptor | A2A receptor activation (slower kinetics, higher MW scaffold) | A2A receptor activation (faster kinetics, higher receptor affinity) |
| Dominant downstream effect | ECM remodelling, fibroblast proliferation, collagen synthesis (MAPK pathway) | Anti-inflammatory, tissue repair, microcirculation (NF-κB inhibition, VEGF upregulation) |
| Tissue persistence | Longer — 3D scaffold formation in dermis | Faster absorption — rapid receptor engagement |
| Primary clinical goal | Skin quality, structural regeneration, long-term density | Tissue healing, anti-inflammatory, post-procedure recovery |
| Typical indications | Photo-ageing, skin laxity, scars, density loss | Post-ablative recovery, alopecia, inflammation-driven conditions |
| Typical protocol | 3–4 sessions every 2–3 weeks | 3–4 sessions, interval varies by indication |
| Market nomenclature note | Most injectable ‘PN’ products on the aesthetic market contain high-MW fractions or mixed PN/PDRN fractions — always verify MW data in product IFU | Products labelled PDRN (e.g. Rejuran) typically specify < 1000 kDa fractions |
Mechanism of Action
4.1 Adenosine A2A Receptor Activation
The primary documented mechanism of both PN and PDRN is activation of the adenosine A2A receptor. Deoxyribonucleotide metabolites bind to this receptor on fibroblasts, endothelial cells and keratinocytes, initiating intracellular signalling cascades:[2][4]
- NF-κB and MAPK pathway inhibition → reduced expression of pro-inflammatory cytokines (TNF-α, IL-6)
- Elevation of intracellular cAMP → anti-apoptotic and anti-inflammatory effects
- VEGF upregulation → angiogenesis, improved tissue perfusion
- MMP-1 inhibition → protection of existing collagen network
- Fibroblast proliferation → increased collagen I and III synthesis, ECM remodelling
PDRN, due to its lower MW, shows faster A2A receptor binding and greater enzymatic stability. PN (higher MW) produces a more sustained scaffolding effect and stronger ECM remodelling, persisting longer in the dermis.[1][2]
4.2 Nucleotide Salvage Pathway
A second documented mechanism is the salvage pathway: exogenous DNA fragments are degraded by endogenous nucleases; released purine and pyrimidine bases are reincorporated into cellular nucleotide synthesis. This supports DNA repair and cell proliferation — particularly relevant in post-ablative and wound-healing contexts.[5]
Clinical Indications
Evidence-based indications for PN/PDRN injectable therapy include:[1][2][4]
Hyperpigmentation — melanogenesis inhibition through tyrosinase activity reduction
Photo-ageing and chronological ageing — skin quality, texture and tone improvement
Skin laxity — dermis density and firmness
Acne scars — ECM remodelling, reduction of dermal tethering
Post-ablative recovery (laser, RF, chemical peel) — accelerated healing, reduced erythema and inflammation
Androgenetic alopecia and alopecia areata — follicular stimulation via improved scalp microcirculation and VEGF upregulation[6]
Pre-volumetric tissue preparation — optimising substrate before HA fillers or biostimulators
Periorbital rejuvenation — dedicated lower-viscosity formulations
Injection Protocols
6.1 Standard Face, Neck and Décolletage Protocol
- Sessions: 3–4 treatments at 2–3 week intervals
- Maintenance: 1 session every 1–2 months
- Techniques: serial puncture (nappage), microdroplet, retrograde linear
- Injection depth: mid-to-superficial dermis, 1.5–2 mm
- Products: Plinest / Plinest Fast | PolyPhil | Nucleofill Medium / Strong
6.2 Periorbital Protocol
- Sessions: 3–4 treatments every 10–14 days
- Technique: micro-papular, 0.2–0.5 cm spacing, dedicated low-viscosity formulations
- Products: Plinest Eye | PolyPhil Eye
6.3 Scalp and Alopecia Protocol
- Sessions: 3–4 treatments every 3–4 weeks
- Technique: mesotherapy into superficial scalp layers, 0.5 ml per injection point
- Combination: PN + PRP shows synergistic effect on hair shaft thickness — supported by clinical literature[6]
- Products: Nucleofill Hair | PolyPhil Hair
6.4 Combination Protocols
PN + HA (Hyaluronic Acid) — indicated for patients presenting with simultaneous skin quality loss and volume depletion. Two clinical approaches:
- Sequential: PN first to optimise tissue substrate; HA filler after 2–3 weeks — typically produces a more natural and durable result
- Same-session: both administered in one visit; practical for patients with limited availability
- Hybrid single-product approach: Renefil is a hybrid PN + HA formulation that delivers regenerative and volumetric effects in a single injectable — eliminating the need to coordinate two separate products
PN + Biostimulator (Sculptra, Radiesse) — recommended sequence: PN first (tissue preparation and quality optimisation), biostimulator introduced 2–3 weeks later. PN improves the tissue environment, potentially enhancing the longevity of longer-acting biostimulant results.
PN + PRP — best-evidenced synergy in alopecia protocols; clinical data indicate improved hair shaft thickness with combined therapy vs. PN alone.[6] Also applicable in post-procedure facial revitalisation.
Product Selection Criteria
When selecting a PN or PDRN product for a clinical protocol, the following parameters are clinically relevant:
- Molecular weight: determines dominant mechanism (faster A2A activation vs. sustained ECM scaffold)
- Extraction and purification technology: PN-HPT™ (Mastelli / Croma-Pharma) and HPT (Promoitalia) affect product purity and batch consistency
- Active substance concentration: ranges from ~1.5% (superficial revitalisation) to 2.5% (structural repair, advanced laxity)
- Area specialisation: dedicated periorbital, scalp and body formulations — viscosity, volume and technique are optimised per area
- Regulatory status: all products should be CE-marked medical devices compliant with EU MDR 2017/745
- DNA source: salmon (Nucleofill) vs. trout (Plinest, PolyPhil) — both are clinically established; source may be relevant for allergy screening
PN Products Available at Fräya Med Supply
The following PN product lines are available for licensed aesthetic practitioners at frayamedsupply.com:
| Brand Line | Products | Technology | Key Indication |
|---|---|---|---|
| Nucleofill | Medium (2%), Strong (2.5%), 25, Hair | Salmon DNA, HPT extraction | Photo-ageing, laxity, density loss, scalp |
| Plinest | Plinest, Fast, Eye, Body, Newest | Trout DNA, PN-HPT™ | Full-face revitalisation, scars, periorbital, post-ablative |
| PolyPhil | PolyPhil, Next, Eye, Hair | PN-HPT, EU MDR certified | All skin types, periorbital, scalp — EU-certified single supplier |
| Renefil | Multiple viscosity variants | Hybrid PN + HA formulation | Simultaneous regeneration and volume: PN + HA in a single injectable |
Frequently Asked Questions
References
[1] Cavallini M et al. Polynucleotides in aesthetic medicine: a review. J Cosmet Dermatol. 2023;22(3):732–740. doi:10.1111/jocd.15579
[2] Veronesi F et al. PDRN and VEGF stimulation in wound healing: experimental and clinical findings. Eur J Histochem. 2022;66(s1):3367. doi:10.4081/ejh.2022.3367
[3] Marques AP et al. Proposed nomenclature for polynucleotides and polydeoxynucleotides in aesthetic medicine: MW cut-off at 1500 kDa. J Cosmet Dermatol. 2025;24(2):e16123. doi:10.1111/jocd.16123
[4] Squadrito F et al. The role of the adenosine A2A receptor in PDRN pharmacology. Curr Pharm Des. 2020;26(7):757–764. doi:10.2174/1381612826666200213100004
[5] Lee SH et al. The salvage pathway of nucleotide synthesis and its role in deoxyribonucleotide therapy. Int J Mol Sci. 2021;22(9):4537. doi:10.3390/ijms22094537
[6] Gentile P et al. Effectiveness of PDRN and PRP in androgenetic alopecia: randomised controlled trial. Aesthet Plast Surg. 2023;47(4):1592–1601. doi:10.1007/s00266-022-03141-y
Note: All references are to peer-reviewed publications. Product information should be verified against current Summary of Product Characteristics / Instructions for Use.
Browse PN & PDRN products at Fräya Med Supply: Available exclusively to licensed aesthetic medicine practitioners.
