MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Polynucleotides / PDRN Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Polynucleotides (PN) and polydeoxyribonucleotide (PDRN) are regenerative skin-booster injectables made from purified salmon- or trout-derived DNA fragments (brands include Rejuran, Plinest and Placentex). Injected into the dermis, they are degraded to adenosine and nucleotides that activate the adenosine A2A receptor, boost VEGF and fibroblast activity, and feed the DNA salvage pathway, stimulating collagen, hydration and tissue repair rather than adding filler volume (PMC5405115). The standard aesthetic protocol is about 2 mL (~20 mg) per intradermal session delivered as many tiny microboluses, with 3-4 loading sessions 2-4 weeks apart and maintenance every 6-12 months. A randomized split-face trial (PMID 32248707) and a 2025 systematic review of 219 patients found improved elasticity, hydration and texture with a mild, transient side-effect profile. Injectable PN/PDRN is not FDA-approved in the United States; the subcutaneous reconstitution figures here are an educational measurement reference only, not medical advice.
Reconstitute: Add 2 mL bacteriostatic water → 10 mg/mL concentration.
Typical dose: ~20 mg (2 mL) per session intradermally; 3-4 sessions 2-4 weeks apart
Easy measuring: At 10 mg/mL, 1 unit = 0.01 mL = 0.1 mg (100 mcg) on a U-100 insulin syringe.
Storage: Commercial prefilled PN/PDRN syringes (Rejuran, Plinest, Placentex): refrigerate at 2-8 °C, protect from light, and do NOT freeze. Research-grade lyophilized powder: store frozen at −20 °C; once reconstituted, refrigerate at 2-8 °C and use within roughly 2-4 weeks.
Half-life: ~3.3-3.5 h plasma half-life (intramuscular, human), 80-90% bioavailable; nuclease-degraded and renally cleared, but regenerative signaling persists days to weeks, so sessions are spaced 2-4 weeks apart.
Route: Intradermal microinjection (superficial micro-bolus/skin-whealing), ~2 mL per session. Real products are prefilled liquid; the subcutaneous reconstitution here is a measurement reference only.
Status: Not FDA-approved in the US for aesthetic injection (topical PDRN = unapproved cosmetic); licensed as a device/drug in South Korea and parts of Europe. Educational content, not medical advice.
About Polynucleotides / PDRN
Polynucleotides / PDRN are regenerative "skin-booster" injectables made from purified salmon- or trout-derived DNA polymers that are placed into the dermis to drive collagen production, hydration and tissue repair rather than to add volume like a traditional filler [1][3]. Clinically the real-world route is intradermal microinjection (a superficial skin-whealing or micro-bolus technique), not subcutaneous; the subcutaneous reconstitution figures below are an educational measurement reference used across this site, and most commercial products (Rejuran, Plinest, Placentex) actually ship as ready-to-use prefilled syringes rather than a powder you reconstitute.\n\nThis guide models a 20 mg research vial reconstituted with 2.0 mL of bacteriostatic water (10 mg/mL, 100 mcg per insulin-syringe unit), so one vial conveniently equals one ~2 mL treatment session. A full-face session of 20 mg (2 mL) measures about 200 units — more than one U-100 syringe, which mirrors clinical practice where the 2 mL is split into dozens of tiny intradermal aliquots; a smaller periorbital or localized session of 10 mg (1 mL) measures 100 units.\n\nThe usual Polynucleotides / PDRN dosage schedule is a loading course of 3-4 sessions spaced 2-4 weeks apart, followed by maintenance every 6-12 months [3][4]. Most visible change appears from the second session, with peak effect typically 4-6 weeks after the final session [4].\n\nFrequency: One ~2 mL intradermal session every 2-4 weeks for 3-4 sessions, then maintenance. Polynucleotides / PDRN injectables are not FDA-approved in the United States; this page is educational only and not medical advice.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 2.0 mL of bacteriostatic water into a sterile syringe (this yields 10 mg/mL from a 20 mg vial, so one vial equals one ~2 mL session).
Inject the water slowly down the inner wall of the vial; do not spray directly onto the material, and avoid vigorous shaking or foaming.
Gently swirl or roll the vial until fully dissolved and clear; the result is 10 mg/mL (100 mcg per insulin-syringe unit).
For the educational model, load a U-100 syringe to the units for your session (a 1 mL/10 mg subzone = 100 units; a full 2 mL/20 mg face session = 200 units, drawn across multiple fills).
Educational note: clinically this is placed by superficial intradermal microinjection with a 30-32G needle, distributing the ~2 mL as dozens of tiny boluses or wheals across the treatment zone — not as a single subcutaneous depot; refrigerate any remainder.
Interactive Polynucleotides / PDRN Syringe Calculator
Currently visualizing the 20 mg vial reconstituted with 2 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 20mg dry powder in 2mL water yields 10.00 mg/mL. To evaluate a 250mcg dose, pull to 2.5 units (3 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Induction — full-face/neck session (×3-4, every 2-4 wks) | 20000 mcg (20 mg) | 200 units (2.00 mL) |
| Periorbital / localized delicate-area session | 10000 mcg (10 mg) | 100 units (1.00 mL) |
| Maintenance — single session every 6-12 months | 20000 mcg (20 mg) | 200 units (2.00 mL) |
Administration guidelines: Refer to guidelines | 2 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 20 mg vial.
Peptide Vials (Polynucleotides / PDRN, 20 mg each):
- check8 weeks ≈ 3 sessions ≈ 3 vials (one 20 mg vial per ~2 mL session)
- check12 weeks ≈ 4 sessions ≈ 4 vials — a typical full loading course
- check16 weeks ≈ 5 sessions ≈ 5 vials (loading course plus one early touch-up)
Insulin Syringes (U-100):
- checkEach ~2 mL session is split into ~30-40 intradermal microboluses; budget 2-3 U-100 syringes (refilled) per session
- check8 weeks (3 sessions) ≈ 6-9 syringes; 12 weeks (4 sessions) ≈ 8-12 syringes
- check16 weeks (5 sessions) ≈ 10-15 syringes; clinics typically use a fine 30-32G needle for superficial placement
Bacteriostatic Water (30 mL bottles): Use 2 mL per vial for reconstitution.
- check8 weeks (3 sessions) ≈ 6 mL — well under one bottle
- check12 weeks (4 sessions) ≈ 8 mL; 16 weeks (5 sessions) ≈ 10 mL
- checkA single 30 mL bottle covers an entire loading course with margin to spare
Alcohol Swabs:
- checkSeveral per session: vial top plus thorough antisepsis of the whole treatment zone
- check8 weeks ≈ 15-25 swabs; 12 weeks ≈ 20-35 swabs
- check16 weeks ≈ 25-45 swabs; keep extras for re-prepping the field between passes
Mechanism of Action (MOA)
Polynucleotides (PN) and polydeoxyribonucleotide (PDRN) are long, linear polymers of deoxyribonucleotides — DNA fragments typically 50-1,500 kDa in size — fractionated and highly purified from the sperm and germ cells of salmon trout (Oncorhynchus mykiss) or chum salmon (Oncorhynchus keta) [1][2]. PDRN refers to the lower-molecular-weight, sterilized fragment mixture, while "polynucleotide" products (PN/PN-HPT) emphasize longer, gel-forming chains; both share the same biology. Because the sequences are not species-specific signaling molecules, they act as a biological raw material rather than a conventional receptor-targeted drug.\n\nThe principal mechanism is twofold. First, as PDRN is slowly digested by membrane-bound and plasma nucleases, it releases the nucleoside adenosine, which engages the adenosine A2A receptor on fibroblasts and inflammatory cells. A2A activation raises intracellular cyclic AMP, activates protein kinase A, and downstream upregulates vascular endothelial growth factor (VEGF), driving angiogenesis, fibroblast proliferation, and extracellular-matrix and collagen synthesis while dampening pro-inflammatory signaling [1][2][6]. Second, the liberated purine and pyrimidine bases feed the DNA "salvage pathway," supplying nucleotides to cells whose de-novo synthesis is impaired in damaged, hypoxic or aging tissue, which supports cell proliferation and repair [1][2]. In the dermis this combination is read clinically as improved hydration, elasticity, texture and fine-wrinkle reduction (skin "bio-remodeling") rather than the space-filling effect of a hyaluronic-acid filler [3][4].\n\nPharmacokinetics: after intramuscular dosing in humans, PDRN reaches peak plasma levels at roughly 1 hour, has an elimination half-life of approximately 3.3-3.5 hours, and shows 80-90% bioavailability; it is not metabolized by the liver but is degraded by nonspecific nucleases and excreted largely renally [1]. Importantly, the pharmacodynamic effect greatly outlasts the plasma half-life: the regenerative signaling cascade it triggers persists for days to weeks, which is why intradermal sessions are spaced 2-4 weeks apart and benefits accrue over the course rather than per injection [1][3].\n\nThe real-world aesthetic route is intradermal microinjection (a superficial micro-bolus/skin-whealing technique); deeper subcutaneous or intramuscular routes are used for the wound-healing and orthopedic indications PDRN is also studied in. The subcutaneous reconstitution scheme on this page is an educational measurement convention only. Injectable PN/PDRN is licensed as a device or drug in South Korea, parts of Europe and several other countries, but is not FDA-approved in the United States for aesthetic injection; it is presented here for educational purposes, not as medical advice [5].
Clinical Trial Efficacy Highlights
- starSquadrito and colleagues (2017, Frontiers in Pharmacology) reviewed the pharmacology of PDRN, establishing that its regenerative effects are mediated by adenosine A2A-receptor activation plus the nucleotide salvage pathway, that it has a plasma half-life of about 3.5 hours with 80-90% intramuscular bioavailability, and that post-marketing surveillance across more than 300,000 prescriptions showed an excellent tolerability profile [1].
- starLee and colleagues (2022, Journal of Dermatological Treatment) ran a randomized, double-blind, split-face trial in 27 subjects who received three polynucleotide-filler sessions on one periocular side and non-crosslinked hyaluronic acid on the other at two-week intervals; global aesthetic scores improved comparably, while the polynucleotide side showed higher improvement rates in skin elasticity, hydration, roughness and pore volume, with no serious adverse events [3].
- starLampridou and colleagues (2025, Journal of Cosmetic Dermatology) systematically reviewed nine clinical studies covering 219 patients treated with polynucleotides for skin rejuvenation and concluded that PN is a natural, effective and safe option that promotes collagen production and improves skin quality, while cautioning that standardized treatment protocols are still lacking and the underlying evidence is of low-to-moderate quality [4].
- starSquadrito and colleagues (2014, Journal of Clinical Endocrinology & Metabolism) conducted a randomized, double-blind, placebo-controlled trial of perilesional and intramuscular PDRN in chronic diabetic foot ulcers (n=216); complete healing occurred in 37.3% of PDRN-treated patients versus 18.9% on placebo, with a faster median time to closure, demonstrating genuine tissue-repair activity beyond cosmetic endpoints [5].
- starGaleano and colleagues (2021, Pharmaceuticals) summarized in-vitro, animal and clinical evidence that PDRN accelerates impaired skin wound healing by increasing VEGF expression, fibroblast proliferation and collagen deposition while reducing inflammatory infiltrate, supporting the same A2A-receptor and salvage-pathway biology exploited in aesthetic skin boosters [2].
- starOh and colleagues (2025, Biomaterials Research) reviewed PDRN across neuromuscular, cutaneous and bone regeneration, describing adenosine-receptor-driven proliferation and anti-inflammatory signaling (including Wnt/β-catenin and NF-κB modulation) and the growing use of PDRN-loaded scaffolds and skin-booster formulations [6].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningInjection-site reactions are the most common effect: transient redness, swelling, small papules or 'whealing,' tenderness and bruising at the intradermal entry points, usually resolving within hours to a few days [3][4].
- warningMild itching and a sensation of skin tightness can occur in the days after a session as the regenerative response develops [4].
- warningLumps, nodules or visible deposits can result from overly superficial, uneven or high-volume placement; these are technique-dependent and usually transient but are a recognized risk of any intradermal microbolus injectable.
- warningAny injectable carries a risk of bacterial infection, and rare hypersensitivity or granulomatous reactions are possible; strict sterile technique and single-use product are essential.
- warningBecause PN/PDRN is derived from salmon and trout DNA, it is contraindicated in people with known fish or seafood allergy or hypersensitivity to the product; an allergy history should be screened before treatment.
- warningTreatment is generally avoided over active skin infection, inflammatory acne or a herpes-simplex outbreak at the site, and during pregnancy or breastfeeding, where safety data are lacking.
- warningPolynucleotides are bio-remodeling agents, not space-filling fillers — they will not correct deep folds or add structural volume, and 'filler-like' expectations are a common source of dissatisfaction [3].
- warningRegulatory/research status: injectable PN/PDRN is NOT FDA-approved in the United States for aesthetic use (topical PDRN is sold only as an unapproved cosmetic); availability elsewhere is as a device or drug, and the figures on this page are educational, not medical advice [5].
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Polynucleotides / PDRN dosage?expand_more
In aesthetic practice the typical Polynucleotides / PDRN dosage is about 2 mL (roughly 20 mg of polynucleotide) per session, placed into the dermis as dozens of superficial microboluses across the treatment area. A standard loading course is 3-4 sessions spaced 2-4 weeks apart, followed by maintenance every 6-12 months. Smaller or delicate zones such as the under-eye area often use about 1 mL (~10 mg) per session. Product concentrations differ between brands (for example Plinest, Rejuran and Placentex), so the exact milligrams per syringe vary; the figures here are an educational reference, not a prescription.
Is Polynucleotides / PDRN FDA approved?expand_more
No. Injectable PN/PDRN skin boosters such as Rejuran and Plinest are not FDA-approved in the United States for aesthetic injection. Injectable PDRN is, however, licensed as a medical device or drug in South Korea, parts of Europe and several other countries. Topical PDRN serums and creams are sold in the US only as cosmetics, which do not receive FDA approval and cannot make medical claims. This page is educational and not medical advice.
What is the half-life of Polynucleotides / PDRN?expand_more
PDRN has a plasma elimination half-life of approximately 3.3-3.5 hours after intramuscular administration in humans, with peak levels around 1 hour and roughly 80-90% bioavailability. It is not metabolized by the liver; instead it is broken down by nonspecific plasma and membrane nucleases and excreted largely through the kidneys. Crucially, the pharmacodynamic effect lasts far longer than the half-life: the regenerative signaling cascade it triggers persists for days to weeks, which is why sessions are spaced 2-4 weeks apart.
How is Polynucleotides / PDRN reconstituted and administered?expand_more
Most commercial PN/PDRN products are sold as ready-to-use prefilled liquid syringes, so no reconstitution is needed in real-world use. For the educational model on this site, a 20 mg vial is mixed with 2.0 mL of bacteriostatic water to give 10 mg/mL (100 mcg per insulin-syringe unit); draw the water slowly down the vial wall, swirl gently until clear, and refrigerate. Administration is by superficial intradermal microinjection with a fine 30-32G needle, distributing the ~2 mL across many tiny boluses or wheals rather than as a single subcutaneous depot.
Can Polynucleotides / PDRN be combined with other treatments?expand_more
In aesthetic clinics PN/PDRN is often layered with hyaluronic-acid skin boosters or fillers, exosomes, microneedling, or energy devices such as lasers and radiofrequency, with the idea that PDRN improves skin quality and repair while other agents add volume or stimulate collagen differently. However, the supporting evidence is limited and treatment protocols are not standardized, so spacing, sequencing and total dosing should be individualized by a qualified provider. There is no validated stacking protocol; treat any combination as experimental, and remember this content is educational only.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Polynucleotides / PDRN, plus the universal dosing calculator.
Academic References & Study Citations
Squadrito F, Bitto A, Irrera N, Pizzino G, Pallio G, Minutoli L, Altavilla D. Pharmacological Activity and Clinical Use of PDRN (Polydeoxyribonucleotides). Front Pharmacol. 2017;8:224. View Scientific Paper →
Galeano M, Pallio G, Irrera N, et al. Polydeoxyribonucleotide: A Promising Biological Platform to Accelerate Impaired Skin Wound Healing. Pharmaceuticals (Basel). 2021;14(11):1103. View Scientific Paper →
Lee YJ, Kim HT, Lee YJ, et al. Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial. J Dermatolog Treat. 2022;33(1):254-260. View Scientific Paper →
Lampridou S, Bassett S, Cavallini M, Christopoulos G. The Effectiveness of Polynucleotides in Esthetic Medicine: A Systematic Review. J Cosmet Dermatol. 2025;24(2):e16721. View Scientific Paper →
Squadrito F, Bitto A, Altavilla D, et al. The effect of PDRN, an adenosine receptor A2A agonist, on the healing of chronic diabetic foot ulcers: results of a clinical trial. J Clin Endocrinol Metab. 2014;99(5):E746-E753. View Scientific Paper →
Oh N, Hwang J, Kang MS, Yoo CY, Kwak M, Han DW. Versatile and Marvelous Potentials of Polydeoxyribonucleotide for Tissue Engineering and Regeneration. Biomater Res. 2025; doi:10.34133/bmr.0183. View Scientific Paper →
Polydeoxyribonucleotide. Wikipedia. Overview of source (salmon/trout sperm DNA), molecular weight, A2A-receptor mechanism, salvage pathway, and clinical use. View Scientific Paper →