Polynucleotides (PN) as a Lip Booster! Discussion of 3 Recent Studies.

Recently, I’ve been curious about using skin boosters in the lips to add hydration and improve the appearance of the lips. I’ve been experimenting with micro droplet injections of polynucleotides and other skin boosters in my lips when I do mesotherapy sessions.

I wanted to share some information from three studies that discuss the efficacy of the use of polynucleotides (PN) in the lips as a booster! This is exciting to me because I think it’s a great alternative to cross-linked HA filler and a nice option for anyone who wants to improve the appearance and feel of their lips while maintaining a natural look without adding volume. Or, if wanting to use alongside hyaluronic acid, some studies have shown that PN may have synergistic benefits when used alongside HA.

Okay, onto the studies------

1) “An Innovative Lip Boosting Technique Using Polynucleotides: “4-point Cannula Technique” (Adel 2025)

This case report evaluates the efficacy of injecting polynucleotides into the lips for lip rejuvenation. Five female patients were included in the study. The intent was to provide a lip hydration effect without adding volume. Patients were injected with PN (1 ml of Rejuran) using a 23g 30mm micro-cannula. Standard photos were taken before and after the injection procedure to evaluate results.

Results and Conclusions:

All patients reported a high degree of satisfaction immediately after the PN injections and there was a marked improvement in lip texture and elasticity that lasted 6 months after the procedure. The author concludes that using PN as a skin booster for lip rejuvenation can provide a hydrating effect without volumization, in addition to improving lip texture. He argues that the use of products such as PN and exosomes should be part of a shift in practice from the direct application of synthetic substances and a reliance on the use of filler, to a cell-signaling approach that aims to stimulate fibroblasts and other cellular components. The study group used was small, but I think this is a great paper! Note that they also provide a lot of detail on the exact injection protocol used in the study (see below).

Diagram showing the 4-point lip injection technique using Rejuran. The black dots represent the entry points for the cannula advancement, the yellow dots represent the microbolus-injected material, and the blue lines represent the retrograde lateral injections (in case needed, as this step was not performed in all patients).

Short video demonstrating the 4-point injection technique (you can also watch or download the video file here https://pmc.ncbi.nlm.nih.gov/articles/PMC11884830/figure/video1/:

Video displays the PN injection with a cannula using the 4-point cannula technique.

2) “Combination of Hyaluronic Acid and Polynucleotides Injection for the Treatment of Cheilitis Simplex” (Ruchiatan et al. 2025)

In this case report study, researchers explored the efficacy of using a combination of PN and HA to treat cheilitis simplex (commonly known as chapped lips, an inflammatory condition characterized by dryness, scaling, and cracking). A female patient diagnosed with cheilitis simplex was treated with a single subdermal injection of a lip booster comprising active ingredients of 1% non-cross linked hyaluronic acid (HA) and 1% polynucleotides (PN), with 0.3% lidocaine as anesthetic agent (product used was Rejuran HB plus). The injection was administered in five points over the four quadrants of the lips (total of 20 points for the entire lips) using a 4mm 33g needle.

Results and Conclusions:

Lip hydration increased gradually, with peak rate of hydration two weeks after injection, and a gradual decrease in hydration until six weeks after injection. The rate of hydration remained higher than the baseline value after this period. Additionally there was an increase in brightness and a shift in pigmentation towards a “rosier hue" as measured by spectrometer analysis.

The authors conclude that the mechanism of HA and PN provide hydration and stimulate dermal fibroblast activity. Also PN may have an additional effect of improving lip pigmentation by reducing melanin and increasing hemoglobin levels. Thus, injection of HA and PN is a practical option for treating cheilitis simplex with additional aesthetic benefits (they state further studies are required to confirm the findings).

(A) Location of the subdermal 1% PN, 1% HA, and 0.3% lidocaine injections at the periphery of the lips (yellow dots). Injection site reaction consisted of: (B) swelling and throbbing pain within 30 minutes after the injection, and (C) bruising (blue arrows) that appeared at 1 day after the injection and started to fade at 3 days after the injection.

3) “Clinical Efficacy and Safety of a Highly Purified Polynucleotide for Dry and Chapped Lips: A Prospective, Multicenter Study” (Rho et al. 2025)

In this prospective study, researchers aimed to determine if PN injections help relieve lip dryness and assess safety in using PN in the lips. 30 subjects with dry and chapped lips received PN injections in the vermilion zone (a total of 3 injections, spaced 3 weeks apart). 1 ml of product (Rejuran) was administered using 12 injection points and 4mm 33g needles. Vermilion wrinkles and roughness were scored based on photos taken  pretreatment (week 0); before the 2nd and 3rd injection (week 3, week 6); and 3 weeks after the 3rd injection (week 9) using severity rating scales. Safety data were obtained throughout the study period.

Results and Conclusions:

PN significantly improved both the vermilion wrinkles and roughness at all time points compared to baseline. Injection site adverse reactions were mostly mild and transient. The authors state their results suggest that PN may be a promising treatment for dry and chapped lips.

Points of administration. All treatments were performed using a multiple puncture technique, where equal amounts of PN were delivered subcutaneously at 12 points.

3D photos at baseline (A, C, E, G) and 3 weeks after the 3rd filler injection (B, D, F, H). The WSRS score changes are as follows: A 4 → B 1, C 4 → D 3, E 3 → F 1, G 3 → H 2. The LRGS score changes are as follows: A 3 → B 0, C 6 → D 2, E 4 → F 0, G 7 → H 1. WSRS score of ≥ 2 points (1—“minimal”, 2—“slight”, 3—“moderate”, 4—“severe”, 5—“extreme lip wrinkles”). LRGS scores (0—“No dryness or chapping evident”, 1‐2—“Slight, but definite roughness; fine scaling”, 3‐4—“Moderate roughness; coarse scaling; slight cracking, 5‐6—“Marked roughness; coarse scaling; obvious cracking, 7‐8—“Very marked roughness; coarse scaling; cracked progressing to fissuring).

Citations and links to articles:

Adel N. An Innovative Lip Boosting Technique Using Polynucleotides: "4-point Cannula Technique". Plast Reconstr Surg Glob Open. 2025 Mar 6;13(3):e6567. doi: 10.1097/GOX.0000000000006567. PMID: 40051974; PMCID: PMC11884830.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11884830/

Ruchiatan K, Yogya Y, Arifani I, Hindritiani R, Puspitosari D, Rizqandaru T, Gondokaryono SP, Achdiat PA. Combination of Hyaluronic Acid and Polynucleotides Injection for the Treatment of Cheilitis Simplex. Clin Cosmet Investig Dermatol. 2025 Dec 29;18:3645-3652. doi: 10.2147/CCID.S571184. PMID: 41488547; PMCID: PMC12758131.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12758131/

Rho NK, Park HJ, Kim HS. Clinical Efficacy and Safety of a Highly Purified Polynucleotide for Dry and Chapped Lips: A Prospective, Multicenter Study. J Cosmet Dermatol. 2025 May;24(5):e70224. doi: 10.1111/jocd.70224. PMID: 40402866; PMCID: PMC12097517.

https://pmc.ncbi.nlm.nih.gov/articles/PMC12097517/