Polynucleotides under eyes are an emerging skin-quality treatment being studied for age-related periorbital concerns. Early research suggests that they may improve hydration, elasticity, texture, and fine lines, although the evidence remains limited and they do not replace treatments for structural hollows, pronounced puffiness, or all causes of dark circles.
The infraorbital area has thin, delicate skin that can be affected by aging, UV exposure, genetics, facial movement, and environmental stressors. These factors may contribute to reduced elasticity, dryness, fine lines, uneven pigmentation, visible vessels, and puffiness. Polynucleotides are intended to support skin-quality and tissue-remodeling processes, but their ability to improve each concern varies.
This guide reviews PN treatment, potential benefits, side effects, reported injection approaches, patient-selection considerations, and contraindications. It is intended for educational purposes and should not replace current product information, clinical training, or professional judgment.
Key Takeaways
- Experimental and early clinical evidence suggests that polynucleotides may influence fibroblast activity, extracellular matrix remodeling, hydration, and inflammatory pathways.
- Claims about increased collagen production or angiogenesis should be described as proposed mechanisms rather than established clinical outcomes.
- Polynucleotides may be considered for selected patients with periorbital fine lines, dryness, mild texture changes, and reduced elasticity.
- Evidence for dark circles, skin laxity, and photodamage is less established and depends on the underlying cause.
- The treatment is contraindicated in people with fish allergies, pregnancy, or those who are breastfeeding.
- Clinical trials indicate that polynucleotide fillers outperform hyaluronic acid fillers in improving skin elasticity and wrinkle reduction around the eyes.
What Is Polynucleotide Treatment for Under Eyes?
Recent aesthetic products contain purified polynucleotides or related DNA-derived materials obtained from salmonid sources, such as salmon or trout. These injectables are generally marketed as skin-quality treatments rather than conventional fillers that create substantial structural volume. Formulations and regulatory classifications vary by product and market, such as trending polynucleotides hair restoration.
Polynucleotide udner eye treatment or products contain long chains of linked nucleotide units, and their molecular weight and physical properties vary by formulation. Specific values, such as a chain length of more than 13 units or a molecular weight of up to 800 kDa, should be retained only when confirmed in the current product documentation [1].
Clinical studies have reported potential benefits and generally favorable short-term tolerability for some polynucleotide products used in skin rejuvenation. However, study quality, product formulations, treatment protocols, follow-up periods, and outcome measures vary, so the evidence should be considered promising rather than definitive.
A clinical report involving 143 patients treated with a long-chain polynucleotide gel described improvements in skin elasticity and hydration, together with favorable patient and physician assessments [2]. Reported outcomes varied by age group and included changes in pore appearance, skin thickness, tone, melanin-related measures, wrinkles, and firmness. Because the study involved a specific product and may not have been a controlled comparative trial, these findings should not be generalized to every PN formulation or presented as proof of efficacy.
How Do Polynucleotides Under Eyes Work?
The proposed mechanisms of polynucleotides involve interactions with dermal cells and the extracellular matrix that may support hydration, tissue remodeling, and repair-related pathways. These mechanisms are biologically plausible, but the exact relationship between laboratory findings and visible clinical results remains under investigation.
Laboratory and early clinical evidence suggests that some polynucleotide preparations may influence fibroblast activity and the production or organization of extracellular matrix components. The magnitude of these effects may depend on the formulation, concentration, injection technique, and patient.
Experimental studies have examined the effects of PN or related PDRN preparations on fibroblast activity, UV-related cellular injury, and collagen-related pathways. These findings help explain the proposed mechanism, but they do not establish that an under-eye injection will reliably increase collagen types I and III or reduce wrinkles in every patient.
In vivo and ophthalmic studies of related PDRN preparations have examined wound healing and corneal epithelialization [3]. These findings provide biological context but should not be interpreted as direct clinical evidence that periocular PN injections treat cosmetic under-eye concerns.
Some experimental research suggests that PN or PDRN may influence angiogenesis-related signaling, including VEGF pathways. However, increased blood-vessel formation is not an established cosmetic treatment outcome and should not be assumed to improve all forms of dark circles or aging skin. Under-eye pigmentation may be epidermal, vascular, structural, or mixed, and requires appropriate assessment.
These properties allow for the following polynucleotides under eyes benefits:
- Improved hydration.
- Possible improvement in elasticity.
- Smoother texture.
- Reduced appearance of selected fine lines.
- Possible reduction in mild inflammation-related redness.
- Improved overall skin quality in selected patients.
Indications for Polynucleotide Treatment Under Eyes
PN treatment may be considered by some qualified providers for:
- Patients seeking possible improvement in mild periorbital fine lines and skin texture, after discussing the treatment’s limitations and uncertain long-term efficacy.
- Selected patients with mild uneven tone or thin, dry under-eye skin may be considered for treatment, but PN should not be presented as a proven treatment for vascular or pigmentary dark circles. Practitioners should assess the cause of dark circles before treatment.
- Patients with mild laxity or reduced skin quality may be considered for treatment, although PN is not a substitute for surgery or a volumizing filler when laxity results from significant tissue descent or volume loss.
- Patients with dry or mildly photodamaged skin may experience improved skin hydration or texture, but established photoprotection and dermatologic treatments may still be required.
- Patients seeking a minimally invasive option for selected skin-quality concerns, provided they understand the potential benefits, limitations, risks, and alternatives.
Contraindications for Polynucleotide Treatment Under Eyes
PN treatment may be well tolerated in many patients, but the polynucleotide treatment for the under-eye area is anatomically sensitive and requires careful patient selection. Providers should review contraindications, medications, allergies, prior procedures, and active skin or eye conditions before treatment.
- Individuals with known hypersensitivity to fish proteins should avoid treatment due to potential allergic reactions
- PNs are not recommended for pregnant or breastfeeding women due to insufficient safety data
- The presence of bacterial, viral, or fungal infections in the treatment area increases the risk of complications
- Individuals with bleeding disorders or on anticoagulant therapy are at higher risk of hematoma formation
Because many PN products are derived from salmonid DNA, they are not vegan. Patients should verify the source and manufacturing information of the specific product if this consideration is important to them.
Furthermore, additional assessment may be needed for patients with a history of severe allergies, autoimmune disease, active dermatitis, uncontrolled diabetes, impaired healing, or previous reactions to injectable products. Product-specific contraindications and local regulations should always take priority.
Are Polynucleotides Better Than Fillers?
Lee et al. conducted a randomized, double-blind, split-face trial comparing a polynucleotide product with a non-crosslinked hyaluronic acid product for periocular rejuvenation. The study included 27 participants, each receiving three treatments at two-week intervals, with PN on one side and HA on the other.
Twenty-seven participants received PN on one side of the periocular area and non-crosslinked HA on the opposite side. Both sides served as active treatment sites; this study did not include an untreated control side. Both products improved selected measures of elasticity and hydration. The PN side showed higher improvement rates for some outcomes, including roughness and pore volume, while overall aesthetic-improvement scores did not differ significantly between the two sides [4]. No serious adverse events were reported.
Meanwhile, an older randomized, double-blind study compared a PN product with HA for crow’s-feet wrinkles and reported improvements in both groups during follow-up. The PN group showed favorable durability at later assessment, but the study’s product, population, and protocol should not be generalized to every current PN or HA injectable. A broader evidence review is still needed before declaring PN superior for all periocular indications.
Current evidence suggests that PN and HA can both improve selected periocular skin-quality measures. One small head-to-head trial found more favorable results for PN on some secondary measures, but overall aesthetic improvement was similar. The available evidence is not sufficient to conclude that PN is universally better than HA fillers around the eyes.
How Are Polynucleotides Administered Under Eyes?
A 2021 consensus report described intradermal PN-HPT™ treatment using small deposits in the periocular area. However, the product concentration, volume, injection depth, technique, and treatment interval vary by formulation and protocol. A recent real-world study used PN-HPT at 7.5 mg/mL, with 1 mL per periocular side and three sessions four weeks apart [5].
The following administration technique has been reported in a trial treating infraorbital dark circles using a polynucleotide filler:
- Injection technique—Intradermal administration using a 33-gauge nanoneedle
- Method—Serial puncture technique with injections spaced about 1 cm apart in the infraorbital region
- Dosage—Total volume ranged from 0.1 to 0.5 ml per side
- Injection volume—Approximately 0.01 to 0.02 ml of PN filler per injection site
- Injection points—12 to 24 sites per infraorbital area
- Post-treatment response—Immediate formation of lumps, which resolved spontaneously within 1-2 days
What Are the Side Effects of Polynucleotides in the Eyes?
Polynucleotides under eye side effects are not serious since it is a minimally invasive treatment. But some patients may experience mild to moderate adverse effects, including:
- Erythema
- Pruritus
- Edema
- Ecchymoses
- Transient irritation
- Infraorbital lumps
Source High-Quality Polynucleotides From Medica Depot
Healthcare professionals seeking a polynucleotide-based gel injection can review NucleoFill, which is available through Medica Depot, subject to product availability and applicable purchasing requirements.
NucleoFill is listed as a polymerized polynucleotide product supplied in a 1 mL pre-filled syringe at a stated concentration of 20 mg/mL. Providers should confirm product composition, indications, storage requirements, and availability using current manufacturer documentation before purchase or clinical use.
Schedule a consultation with our sales team today to learn how to procure NucleoFill for your practice and keep your clients safe and satisfied. Schedule a consultation with our sales team to review product availability, purchasing requirements, and information relevant to your practice. Clinical use should follow applicable regulations, product instructions, and professional training.
Citations
[1] Lee, Dagyeong, et al. “Current Practices and Perceived Effectiveness of Polynucleotides for Treatment of Facial Erythema by Cosmetic Physicians.” Skin Research and Technology, vol. 29, no. 9, Sept. 2023, p. e13466. https://doi.org/10.1111/srt.13466.
[2] Cavallini, Maurizio, and M. Papagni. “Long Chain Polynucleotides Gel and Skin Biorevitalization.” ResearchGate, Sept. 2007, www.researchgate.net/publication/289215376_Long_chain_polynucleotides_gel_and_skin_biorevitalization.
[3] Lazzarotto, M, et al. “Clinical Evaluation of Corneal Epithelialization After Photorefractive Keratectomy in Patients Treated With Polydeoxyribonucleotide (PDRN) Eye Drops: A Randomized, Double-Blind, Placebo-Controlled Trial.” European Journal of Ophthalmology, vol. 14, no. 4, 2004, pp. 284–89, https://pubmed.ncbi.nlm.nih.gov/15309972/.
[4] Lee, Ye Jin, et al. “Comparison of the Effects of Polynucleotide and Hyaluronic Acid Fillers on Periocular Rejuvenation: A Randomized, Double-blind, Split-face Trial.” Journal of Dermatological Treatment, vol. 33, no. 1, Apr. 2020, pp. 254–60. https://doi.org/10.1080/09546634.2020.1748857.
[5] Cavallini, Maurizio, et al. “Consensus Report on the Use of PN‐HPTTM (Polynucleotides Highly Purified Technology) in Aesthetic Medicine.” Journal of Cosmetic Dermatology, vol. 20, no. 3, Aug. 2020, pp. 922–28. https://doi.org/10.1111/jocd.13679.
This content was prepared and reviewed under our editorial guidelines , which govern how we source, verify, and update clinical and product information. Every claim is checked against peer-reviewed research, manufacturer documentation, or regulatory guidance before publication.



