Polynucleotides, what practitioners should understand

Polynucleotides have moved from curiosity to mainstream in under three years; the evidence base is now strong enough to plan protocols around.

Polynucleotides (PN) and polydeoxyribonucleotide (PDRN) injectables are now among the most discussed topics at UK aesthetic training days and in clinical forums. Yet the terminology is used loosely, formulations differ considerably, and many practitioners are still piecing together a coherent picture from fragments. This guide consolidates the key science, the available clinical evidence, the relevant brand differences, and the patient selection principles that should inform your prescribing and purchasing decisions. It is written for licensed UK practitioners who are already familiar with injectable aesthetics and are evaluating whether and how polynucleotides fit into their treatment menu.

Longeva Pharmacy stocks a curated range of polynucleotide products alongside other skin booster injectables. You can browse the full product range when you are ready to order.

What are polynucleotides?

Polynucleotides are long-chain nucleic acid polymers made up of repeating nucleotide units. In the context of aesthetic medicine, the active molecules are derived from the DNA of salmon or trout (genus Oncorhynchus). Sperm DNA from these fish is highly purified, enzymatically fragmented, and filtered to remove proteins, lipids, and allergenic components. What remains are chains of deoxyribonucleotides, predominantly polyadenine-thymidine (poly-AT) sequences, which are biologically active in human tissue.

The terminology can be confusing. PDRN (polydeoxyribonucleotide) refers to the shorter-chain fractions, typically in the 50 to 2,000 base pair range, that are particularly associated with adenosine A2A receptor activation. PN (polynucleotide) is a broader term that can encompass both short and long chain fractions. Different manufacturers use different chain lengths and purification processes, which partly explains why formulations produce varying clinical effects. Neither PDRN nor PN is the same as hyaluronic acid-based skin boosters, though they are often discussed alongside them.

Mechanism of action

Polynucleotides exert their effects through several complementary pathways.

Adenosine A2A receptor agonism: PDRN fractions bind to adenosine A2A receptors on fibroblasts, macrophages, and endothelial cells. This receptor activation drives downstream signalling that promotes collagen synthesis and downregulates pro-inflammatory cytokines. The anti-inflammatory effect is well characterised in the wound-healing literature and provides the biological rationale for using PN in skin quality improvement.

Salvage pathway substrate: Polynucleotides act as a direct source of nucleotides for the DNA salvage pathway. Cells under metabolic stress, for example in photo-damaged or aged dermis, preferentially use the salvage pathway rather than synthesising nucleotides de novo. Providing exogenous nucleotide chains gives fibroblasts and keratinocytes the raw material they need for repair, proliferation, and matrix production.

Growth factor modulation: Receptor activation leads to upregulation of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which support neovascularisation and fibroblast recruitment. Histological studies have shown increased collagen density and improved elastic fibre organisation in treated tissue.

Tissue hydration: Some formulations contain hyaluronic acid or have hydrophilic properties that confer a hydrating effect in the short term, though the primary mechanism of polynucleotides is regenerative rather than volumising.

The evidence base

The polynucleotide evidence base is growing but remains weighted towards in vitro studies, animal models, and smaller clinical trials. Practitioners should understand what the data does and does not show.

A notable peer-reviewed study by Mastropasqua and colleagues published in Nature Scientific Reports (2020) investigated PDRN in ocular surface repair. The study demonstrated upregulation of VEGF and collagen synthesis markers consistent with the A2A receptor mechanism described above (Mastropasqua et al., Nature Scientific Reports, 2020). While this research focused on ophthalmic tissue, the receptor biology and cellular response mechanisms are directly relevant to dermal applications.

Clinical evidence specific to aesthetic indications includes randomised controlled trials on PDRN for acne scarring, photodamage, and skin laxity. These studies consistently show improvements in skin texture, elasticity, and hydration scores versus control. Effect sizes are moderate, onset is gradual over four to eight weeks, and durability at six months appears clinically meaningful where reported. However, most trials use small sample sizes, and head-to-head comparisons between branded formulations are largely absent from the peer-reviewed literature.

The British College of Aesthetic Medicine (BCAM) includes polynucleotides within its overview of injectable treatments and notes the need for practitioners to evaluate evidence critically and maintain appropriate training (BCAM treatment information). Practitioners working under JCCP standards should ensure their consent processes and clinical governance reflect the evidence level for each indication.

In summary, the mechanism is well-supported and the clinical signal is consistent. The evidence is strong enough to inform routine protocols, though practitioners should set realistic expectations with patients and document their clinical rationale.

Formulation and concentration differences across brands

Not all polynucleotide products are identical. Understanding the formulation differences helps practitioners select the most appropriate product for a given indication.

PhilArt (Croma): A purified PDRN gel in a viscoelastic carrier. Manufacturer information for PhilArt describes a high-viscosity formulation designed for intradermal and subdermal placement. The concentration and chain length are calibrated for structural indications as well as skin quality work. Available in different viscosities within the range.

PolyPhil (Croma): A sister product in the Croma polynucleotide line with a formulation optimised for fine-line and superficial intradermal placement. The lighter consistency is suited to periocular, perioral, and thin-skin areas where heavier gels may cause visible product.

Ameela: A CE-marked polynucleotide injectable that has achieved significant uptake in the UK market. The formulation emphasises skin biorevitalisation. Practitioners report a smooth injection experience with the 27-gauge needle provided.

Plenhyage: An Italian-origin PDRN product with a longer clinical track record in Europe. Available in standard and XL (higher concentration) variants. The XL variant is often used in more severe photodamage or when a stronger regenerative stimulus is desired.

Lumi Eyes: Specifically indicated and widely used for periocular rejuvenation, including under-eye hollowing and dark circles with a textural component. Not appropriate where significant volume deficit is the primary concern.

Across all brands, practitioners should review the product information, confirm CE marking and appropriate regulatory status for the UK market, and store according to manufacturer instructions, typically refrigerated and used within the stated shelf life after opening.

Patient selection and indications

Polynucleotides are best positioned as a skin quality and regenerative treatment. Appropriate patient selection significantly affects outcome satisfaction.

Strong candidates include patients presenting with: dull or dehydrated skin that does not respond well to topicals alone; fine lines related to skin laxity and reduced collagen density rather than repetitive muscle action; photodamage with uneven texture and mild pigmentation; thin or crepey skin around the eyes, neck, or decolletage; post-procedure recovery where accelerated healing is a clinical goal; and patients who have had previous filler and want to improve the quality of the surrounding tissue rather than add more volume.

Age range: The literature does not restrict polynucleotides to a specific age group. The A2A receptor mechanism is relevant wherever fibroblast activity is reduced and oxidative stress is a driver, which can begin from the mid-30s in photoexposed patients. Conversely, younger patients with acne scarring or post-inflammatory hyperpigmentation may also benefit.

Skin types: Evidence is available across Fitzpatrick types I to VI, though specific brand studies may skew to lighter skin types. Periocular applications require particular care in darker skin types given the proximity of vessels.

What polynucleotides are not

Clarity on what these products cannot do is as important as understanding what they can.

Polynucleotides are not volumisers. They do not replace lost soft tissue volume or provide structural lift. A patient with significant malar hollowing or deep nasolabial folds driven by volume loss needs a different treatment modality. Positioning PN as a filler substitute will lead to patient dissatisfaction.

They are not a replacement for anti-wrinkle treatment where dynamic movement is the primary driver of a line. The regenerative mechanism operates on the quality of the dermis, not on neuromuscular function.

They are also not a rapid-result treatment. Clinical improvement is typically visible at four to six weeks and continues to develop over several months. Patients conditioned to expecting immediate post-treatment change need clear briefing before their first session.

Treatment protocol and intervals

There is no single universally mandated protocol for polynucleotides. The following represents the consensus approach derived from manufacturer recommendations and published clinical practice guidelines.

Course structure: Most brands recommend a primary course of three to four sessions spaced two to four weeks apart. This induction phase allows cumulative fibroblast stimulation to build. Single-session outcomes are typically modest and should not be used to judge the full potential of the treatment.

Maintenance: Following the induction course, most patients benefit from one to two maintenance sessions per year. Some practitioners in high-photodamage patient populations move to three maintenance sessions annually.

Technique: Injection technique varies by product viscosity and target tissue. Common approaches include serial threading, retrograde linear, and depot injection. Depth should match the product and the indication: superficial intradermal for fine lines and periocular work, deeper dermal for skin laxity on the face, neck, and decolletage. Always refer to the specific product's injection technique guidance.

Combination protocols: Polynucleotides are commonly used alongside energy-based devices and topical programmes. The regenerative stimulus from PN may be potentiated by concurrent microneedling or radiofrequency, though practitioners should stagger treatments appropriately and manage any inflammatory response. There is no contraindication to combining with hyaluronic acid skin boosters in the same course, though same-session combination is a practitioner judgement call not universally endorsed in the literature.

Contraindications and safety

The safety profile of polynucleotides is generally favourable, with the principal risks those common to all injectable aesthetics rather than specific to the product class.

Absolute contraindications: Known hypersensitivity to salmon or fish-derived products. Patients with active skin infection at the intended injection site. Autoimmune conditions in active flare where immune modulation is a concern (seek specialist guidance). Pregnancy and breastfeeding, on precautionary grounds in the absence of safety data.

Relative contraindications and cautions: Patients on anticoagulants or antiplatelet therapy have increased bruising risk and should be counselled accordingly. History of hypertrophic or keloid scarring warrants careful assessment. Roaccutane (isotretinoin) use within six months is a relative contraindication due to impaired wound healing, consistent with general guidance for injectable and resurfacing treatments.

Common side effects: Injection site redness, swelling, and bruising are expected and typically resolve within 48 to 72 hours. Papule formation at injection sites, particularly with superficial placement, can persist for one to two weeks. Patients should be warned and reassured.

Vascular complications: As with all facial injectables, vascular occlusion is a theoretical risk. Practitioners must have appropriate training, maintain emergency protocols, and hold hyaluronidase where HA products are in use. PN products do not dissolve with hyaluronidase, but the general vascular safety framework applies.

All practitioners offering injectable treatments in the UK should be registered with a recognised professional body and working within the JCCP framework or equivalent standards. The BCAM provides additional guidance on clinical governance for aesthetic practitioners.

Key takeaways

• Polynucleotides are derived from highly purified salmon or trout DNA and act primarily via adenosine A2A receptor agonism and nucleotide salvage pathway support.
• The mechanism is well-characterised. Published clinical evidence, including peer-reviewed work such as Mastropasqua et al. (2020), supports the regenerative and anti-inflammatory effects.
• Formulations differ in chain length, viscosity, and concentration. PhilArt, PolyPhil, Ameela, Plenhyage, and Lumi Eyes are each suited to slightly different indications and anatomical zones.
• Best results come from a three to four session induction course at two to four week intervals, with annual maintenance thereafter.
• Polynucleotides improve skin quality and support collagen regeneration. They do not replace volume, lift soft tissue, or address dynamic lines driven by muscle action.
• Patient selection matters. Photoaged, dehydrated, or post-procedural skin responds well. Volume-deficient patients should be treated with an appropriate volumiser first or alongside.
• Contraindications include fish allergy, active infection, pregnancy, and active autoimmune flare. Bruising and transient papules are the most common side effects.
• Clinical governance requirements, including appropriate training and consent, apply to polynucleotides as they do to all injectable aesthetics under current UK standards.

References

• Mastropasqua et al. (2020). Polydeoxyribonucleotide effects on human conjunctival fibroblasts. Nature Scientific Reports.
• British College of Aesthetic Medicine (BCAM). Dermal Fillers and Injectables: Patient Information.
• Joint Council for Cosmetic Practitioners (JCCP). Practitioner Standards and Register.
• Croma. PhilArt Product Information (manufacturer prescribing information, available on request from Croma UK).

Reviewed for clinical accuracy under the supervision of our Superintendent Pharmacist, Alicia Barker (GPhC 2241860). Longeva Pharmacy is a GPhC-registered pharmacy (registration 9012378) operating under MHRA WDA(H) licence 59619. Information is intended for licensed UK practitioners and does not replace individual clinical judgement.