Periorbital Polynucleotide Injections

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 by Michael T Yen, MD on November 2, 2025.


Surgical Therapy

The most common use for polynucleotide injections are dermal injections for cosmetic skin rejuvenation. However, they are also also utilized for vulva vaginal atrophy, androgenetic alopecia[1] and intraarticularly in the treatment of knee[2] and temporomandibular osteoarthritis in place of hyaluronic acid.

PN/PDRN injections are marketed as ‘skin boosters’, gaining popularity in the aesthetics industry because they have little-to-no downtime and stimulate action of the body’s own cells.

Cosmetic PN injection are short procedures done in the outpatient setting. Patients are recommended to have a course of 2-3 treatments spaced 2 weeks apart. The results of polynucleotide treatments typically last 6-12 months, after which a top-up dose is recommended.

Polynucleotides can be combined with hyaluronic acid fillers, botox or other modes of skin treatments such as lasers, intense pulse light therapy, radiofrequency or ultrasonic machines such as HIFU. The anti-inflammatory effect of polynucleotides help counter the heat generated by devices when used in the same setting. The concurrent usage of devices can also reduce the appearance of post intradermal injection blebs induced by PN treatment.

Background

Aesthetic injectables were introduced in the 1800s by German surgeon Franz Neuber, who first injected his patients with autologous fat with the aim of facial reconstruction. Over the years, several agents have been used with the aim of rejuvenating and restoring a youthful facial appearance.

The latest development in cosmetic industry are Polynucleotides (PNs) and Polydeoxynucleotides (PDRNs) injectables. They are long chain DNA polymers which are extracted from salmon gonads then filtered, ultra-purified and sterilized. Polynucleotides are polyesters of phosphoric acid with ribose (ribonucleic acids, RNAs) or with 2′-deoxyribose (deoxyribonucleic acids, DNAs).

Polynucleotide injectables act by stimulating fibroblasts to produce collagen and scavenge free radicals, improving appearance of hydrated skin[3]. They also suppress inflammatory pathways (the NF-κB pathway) and lower inflammation markers which protects collagen from degradation[4].

Differences between Polynucleotides and Polydeoxyribonucleotides

Both PN and PDRN are extracted from salmon - PN originates from the salmon testes, whereas PDRN is derived from sperm cells. PN features longer nucleotide chains and a higher molecular weight. PN has a distinct scaffold structure, setting it apart from PDRN formulations.


Patient Selection

Polynucleotide injections are classed as non-essential cosmetic procedures and are carried out on an elective basis, often offered in private aesthetic clinics and carried out by cosmetic practitioners, nurses and aesthetic doctors. They are suitable for both males and females, though are marketed differently to both, with the ultimate end goal of an anti-aging appearance.

Indications

The periorbital region is a popular area for injectables due to visibly reduced volume with aging and development of rhytids due to sun exposure and facial movements. The most common indications of these injections are periorbital and infraorbital fine lines e.g. ‘crows feet’ wrinkles, fine lines on the cheek or nasolabial region, uneven skin texture or hyperpigmentation, dry skin and androgenetic alopecia.

Contraindications

Fish Allergies

Polynucleotide injections should not be offered to patients with fish or shellfish allergies due to their origin. Though this product has been purified in the manufacturing process, a small risk of hypersensitivity remains in patients who are allergic to fish.

Active infection

PNs should be avoided in patients with active infection in the periorbital area such as shingles, orbital or preseptal cellulitis.

Pregnancy or Breastfeeding

There is lack of evidence to demonstrate adverse effects in pregnancy or breastfeeding however practitioners recommend to avoid PN/PDRN injections during this period.

Flare up of allergic reactions

True allergy to polynucleotides are rare however a lot of PN/PDRN products also contain hyaluronic acid filler, which can trigger hypersensitivity and allergic reactions in patients who are sensitive to them. They can have a delayed onset, occurring four to 14 months after injection of the product and are treated with steroids and antihistamines.

Bleeding disorders

PNs are not adviced for peoples with bleeding tendencies or those on anticoagulants due to the risk of arterial injury and hematoma formation. PN treatment is also not a single injection, instead require multiple series of injection points, in many sessions.

Autoimmune disorders

Some practitioners avoid injecting Hyaluronic Acid containing products (these include some PN/PDRN products) in patients with systemic lupus erythematosus or scleroderma due to the theoretical risk of reactivation of the disease.

Injection Techniques

The desired effect of treatment is achieved in multiple sessions. PN injection is delivered under topical anaesthesia, such as Lidocaine 10% numbing cream. The area of injection should be thoroughly cleaned prior to administration of the product. They are injected to the dermis of the skin using a 33 gauge needle, a 25 gauge or 30 gauge cannula. The volume of product delivered ranges from 0.01ml to 0.1ml [5] . In injecting combined filler/polynucleotide products, using a cannula is proven to have a lower rate of vascular occlusion[6]. The following techniques are used:

Linear treading

The cannula or syringe needle is punctured, and product is deposited in a linear fashion. This can be deposited in an anterograde or retrograde pattern. Product is deposited while entering the dermis in the anterograde technique. In the retrograde technique, while withdrawing the needle from the injection site, the plunger is depressed to deposit the product in the tract created by the injection device.

Cross Hatching

The product is injected in a series of parallel lines in the treatment area, then injected 90 degrees perpendicular from first site of injection to create a crosshatch method. It is infrequently used in the infraorbital area due to limited surface area.

Microbolus Technique

The treated area is marked in a grid pattern. Small, regularly spaced blebs are injected into the mid dermis leaving a small gap, typically 1-2cm between each one. This technique is relatively low pressure give a small amount of product injected each time. It is used in larger surface areas such as the temporal region or the cheek.

Serial Puncture Technique

Serial puncture is similar to the microbolus technique in that small amounts of products are injected at any one time (0.01-0.02ml), however this can be targeted to be along a wrinkle or specific areas.

Fanning Technique

The needle in advanced into the dermis and a small amount of product is deposited while withdrawing, as in the linear treading technique. Then the injector changes the angle of the needle radially and repeats this process in a fan-like pattern.

Periorbital Injection Sites

Outcomes

PN/PDRN injections are generally safe and well-tolerated treatments, providing patients with a natural enhancement of their appearance. The redness and swelling associated with the injections reduce in 24-48 hours, allowing patients to resume their daily life. The benefits of skin hydration, subtle firming effect and improved skin texture, which rely on cell turnover, can be detected from as early as the end of the first week to 12th week post-treatment.

Complications

Localized reactions

The most commmon complication of PNs are localised erythema, mild bruising and swelling at the injection site. These subside after a few hours to days. Patients are advised to limit sun exposure, use sunscreen to reduce UV damage, moisturize the skin to protect the skin barrier, avoid heavy exercise, alcohol and saunas.

References

  1. Thanasarnaksorn W, Limsuchaiwat N, Sirithanabadeekul P, Charoensuksira S, Suwanchinda A, Meephansan J. Polynucleotides as a novel therapeutic approach in androgenetic alopecia: an analysis of effectiveness and safety. Archives of dermatological research. 2025;317(1):399. doi:https://doi.org/10.1007/s00403-025-03908-6 ‌
  2. Lee D, Kim W-h, Ha JH, Kim H, Kim J, Shin DW. Current Practices and Perceived Effectiveness of Clinicians Regarding Polynucleotide Injection for Knee Osteoarthritis: A Survey-Based Evaluation. Healthcare. 2025; 13(2):113. https://doi.org/10.3390/healthcare13020113
  3. Kim JH, Kwon TR, Lee SE, et al. Comparative Evaluation of the Effectiveness of Novel Hyaluronic Acid-Polynucleotide Complex Dermal Filler. Sci Rep. 2020;10(1):5127. Published 2020 Mar 20. doi:10.1038/s41598-020-61952-w
  4. Han HS, Shin HR, Kim S, Cho YD. Polynucleotide with cross-linked hyaluronic acid reduces inflammation and increases collagen synthesis. J Periodontal Implant Sci. 2025;55(3):206-216. doi:10.5051/jpis.2402520126
  5. Cavallini M, Bartoletti E, Maioli L, et al. Consensus report on the use of PN-HPT™ (polynucleotides highly purified technology) in aesthetic medicine. J Cosmet Dermatol. 2021;20(3):922-928. doi:10.1111/jocd.13679
  6. Alam M, Kakar R, Dover JS, et al. Rates of Vascular Occlusion Associated With Using Needles vs Cannulas for Filler Injection. JAMA Dermatol. 2021;157(2):174-180. doi:10.1001/jamadermatol.2020.5102
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