Human in vivo
>20 µm into the superficial viable epidermis
Observed 8–24 h. Model: human skin in vivo. n=1. Measurement: Raman spectroscopy.
Relative signal, not a mass balance; n=1.
Molecular Scale
How big PDRN is, how big the skin barrier lets through, and what was actually measured in human skin.
50–1500 kDacommercial PDRN range
500 Daskin-penetration threshold
3.06% at 24 h (n=1)relative permeation
D = 1.55 × 10⁻¹⁰ m²/smeasured diffusion coefficient
How big is PDRN compared to what skin lets through?
PDRN runs 50–1500 kDa, with commercial forms peaking near 350 kDa and the main active band at 80–200 kDa — 100 to 3000 times the 500 Da skin-penetration threshold.
That is a delivery problem, not a verdict. A human in vivo Raman measurement of a 0.1% PDRN eye cream recorded 0% at 4 h, 2.04% at 8 h and 3.06% at 24 h, with signal beyond 20 µm into the superficial viable epidermis (n=1).
The 500 Da rule was built on arguments about small molecules and is not a direct verdict on PDRN (Bos and Meinardi, Exp Dermatol 2000).
01 · The molecular ruler
The scale, with only the data-backed anchors.
Four anchors, one threshold and one measured overlay. No other molecule is placed on this ruler because no citation for one exists in the collected research.
500 Dathe skin-penetration threshold in the field’s rule of thumb
80–200 kDathe primary active band
50–1500 kDacommercial range, with a peak near 350 kDa
not quantifiedlow-molecular-weight fragments; the collected data supplies no number
02 · The depth axis
Three model-specific depth plates.
These are not one continuous curve. Each plate names its model, its n and its measurement type.
Ex vivo porcine
dermis at 8–12 h
Franz diffusion cell with fresh porcine dorsal skin. Model: ex vivo animal. n=3. Measurement: FITC-labelled PDRN, confocal microscopy.
Porcine skin is not human skin; labelling may alter the molecule.
Reconstructed human epidermis
viable epidermal regions
EpiKutis reconstructed human epidermis model. Model: in vitro. n=3. Measurement: confocal Raman, semi-quantitative.
Aqueous model, not the finished formulation.
D = 1.55 × 10⁻¹⁰ m²/s
effective diffusion coefficient in skin · ex vivo micropig membrane, n=3 · used to calibrate the simulation
Simulationeffective diffusion coefficient in skin · ex vivo micropig membrane, n=3 · used to calibrate the simulation
Not one curve. The three measurements use different models and are not directly comparable. The pin positions are schematic, not a shared depth scale. The diffusion coefficient is a model input, not a depth marker.
03 · Measured rate panel
The numbers and the method that produced them.
relative permeation at 4 h / 8 h / 24 h. Raman spectroscopy; single-subject exploratory study. Relative signal, not a mass balance.
effective diffusion coefficient in skin, measured ex vivo in micropig membrane, n=3. It is a simulation input, not a human value.
linear regression of cumulative permeation in the porcine Franz-cell experiment, n=3.
ex vivo porcine skin. This is a model result, not a human clinical endpoint.
04 · The 500 Da rule
An anchor built on small molecules.
The rule’s three original observations are real, and its boundary is equally real.
The three original observations
What the rule was built from.
- Almost all common contact allergens are below 500 Da.
- Most topical dermatological drugs are below 500 Da.
- All known transdermal drug-delivery drugs are below 500 Da.
Bos and Meinardi, Exp Dermatol 2000 (PMID 10839713).
The boundary
What the rule cannot decide.
The rule was not designed with large nucleic-acid molecules in mind. It cannot serve as the direct verdict on whether PDRN penetrates. The measurements above show that PDRN enters the superficial viable epidermis at an extremely low rate.
Closing fact: PDRN at 50–1500 kDa is 100 to 3000 times the threshold, yet 3.06% relative permeation was recorded at 24 h (n=1).
05 · Molecular spec sheet
The full twelve-row sheet.
Grouped by specification type. The low-molecular-weight fragment has no numeric value in the collected data; it is not estimated.
| Specification | Value · extraction | Dermatology relevance | Citation | Confidence |
|---|---|---|---|---|
| Molecular weight · 3 | ||||
| PDRN molecular weight range (commercial form)MW_PDRN_RANGE | 50–1500 kDa · peak ~350 kDa Purified from salmon/trout sperm DNA | The overall range (50-1500 kDa) sits far above the 500 Da skin-penetration ceiling, so the intact PDRN molecule struggles to cross the stratum corneum; commercial forms peak around 350 kDa. Measured penetration is extremely low but not zero: human in vivo Raman shows 3.06% relative permeation at 24 h with signal more than 20 micrometers into the superficial viable epidermis, and ex vivo porcine skin shows dermal arrival at 8-12 h. | high | |
| PDRN primary molecular weight band (active fraction)MW_PDRN_PRIMARY_BAND | 80–200 kDa Predominantly salmon-derived fragments | Although the total range extends up to 1500 kDa, biological activity is concentrated mainly in the 80-200 kDa band. Lower-molecular-weight fragments have shown better biological activity than higher-molecular-weight counterparts. | medium | |
| Low-molecular-weight fragments (higher activity)MW_LOW_FRAGMENT | Not quantified in the collected data Controlled enzymatic degradation | Low-molecular-weight PDRN fragments are associated with better biological activity, cellular uptake and skin penetration. This is the molecular basis for the idea that topical PDRN may still be viable, and is the key molecular argument when comparing the topical route against injection. | medium | |
| Source · 5 | ||||
| Human placenta (historical origin)SOURCE_HUMAN_PLACENTA | — Placental tissue extraction | PDRN was first isolated from human placenta in Italy for pharmaceutical development and has since been largely displaced by salmon and trout sources. Placenta-derived DNA fragments also show wound-repair activity via the A2A receptor in skin models. | high | |
| Salmon (current mainstream)SOURCE_SALMON | >95 Purification of salmon sperm DNA | The industry-standard source because it is readily available, easy to process and yields a highly pure active substance above 95%. The site product database records 98 products with dna_source=salmon. | high | |
| Trout (co-mainstream)SOURCE_TROUT | — Purification of trout sperm DNA | Co-equal with salmon. A head-to-head comparison found no statistically significant difference in wound healing between the two, although their fragment characteristics differ, making them separate entries in any discussion of alternative sources. | high | |
| Plant-derived (emerging)SOURCE_PLANT | — Plant DNA or polysaccharide degradation fragments | Most plant-derived preparations have lower molecular weight than animal-derived PDRN, which is associated with better bioavailability, cellular uptake and skin penetration. The site product database already contains products labelled with plant sources. | medium | |
| Microbial-derived (emerging)SOURCE_MICROBIAL | — Microbial fermentation and extraction of DNA | First reported in 2025 as a sustainable and scalable alternative to salmon-derived PDRN. Still at the research stage, with no corresponding marketed products. | medium | |
| Skin penetration · 1 | ||||
| Skin penetration molecular weight threshold (500 Dalton rule)DA_DALTON_THRESHOLD | ≤ 500 Da Not applicable | Bos and Meinardi (Exp Dermatol 2000) established that molecules under 500 Da can be absorbed through skin. PDRN at 50-1500 kDa is 100 to 3000 times that threshold. This is the foundation of the topical-vs-injectable page. IMPORTANT BOUNDARY: the rule was formulated around small molecules, so it cannot be treated as a direct verdict on whether PDRN penetrates. Measured data show PDRN reaches the superficial viable epidermis at an extremely low rate. | high | |
| Purity · 1 | ||||
| Salmon-derived PDRN purityPURITY_SALMON | >95% Separation and purification of salmon sperm DNA | High purity above 95% is a key metric for reducing immunogenic side effects and is one reason salmon became the industry-standard source. | high | |
| Physical property · 1 | ||||
| Physicochemical properties: polyanionic and hydrophilicCHEM_POLYANIONIC_HYDROPHILIC | — Not applicable | PDRN is a negatively charged, hydrophilic polymer. This adds a second barrier on top of molecular size: passive diffusion through the lipid pathways of the stratum corneum is extremely weak. The effect stacks with the 500 Da threshold rather than replacing it. | medium | |
| Comparative · 1 | ||||
| Structural differences between PN and PDRNPN_VS_PDRN_STRUCTURAL | — Not applicable | PN (Polynucleotide) consists of longer DNA fragments and dominates extracellular matrix remodelling, while PDRN consists of relatively shorter oligonucleotide sequences and drives adenosine receptor activation plus nucleotide synthesis support. Despite structural similarity the two differ in function. This is the primary source behind the site's finding that PN is only partially equivalent to PDRN and carries high confusion risk. | high | |
06 · Source and purity
Five source paths and one purity metric.
The site database records 522 of 644 products with no disclosed source. Source, extraction and purity are separate facts.
Human placenta (historical origin)
Extraction: Placental tissue extraction
PDRN was first isolated from human placenta in Italy for pharmaceutical development and has since been largely displaced by salmon and trout sources. Placenta-derived DNA fragments also show wound-repair activity via the A2A receptor in skin models.
Salmon (current mainstream)
Extraction: Purification of salmon sperm DNA
The industry-standard source because it is readily available, easy to process and yields a highly pure active substance above 95%. The site product database records 98 products with dna_source=salmon.
Trout (co-mainstream)
Extraction: Purification of trout sperm DNA
Co-equal with salmon. A head-to-head comparison found no statistically significant difference in wound healing between the two, although their fragment characteristics differ, making them separate entries in any discussion of alternative sources.
Plant-derived (emerging)
Extraction: Plant DNA or polysaccharide degradation fragments
Most plant-derived preparations have lower molecular weight than animal-derived PDRN, which is associated with better bioavailability, cellular uptake and skin penetration. The site product database already contains products labelled with plant sources.
Microbial-derived (emerging)
Extraction: Microbial fermentation and extraction of DNA
First reported in 2025 as a sustainable and scalable alternative to salmon-derived PDRN. Still at the research stage, with no corresponding marketed products.
Salmon-derived PDRN purity
High purity above 95% is a key metric for reducing immunogenic side effects and is one reason salmon became the industry-standard source.
07 · Physicochemical properties
The third layer of the barrier argument.
Physicochemical properties: polyanionic and hydrophilic
PDRN is a negatively charged, hydrophilic polymer. This adds a second barrier on top of molecular size: passive diffusion through the lipid pathways of the stratum corneum is extremely weak. The effect stacks with the 500 Da threshold rather than replacing it.
Confidence
Size → charge → depth: the three layers stack. Explaining the delivery gap with the 500 Da rule alone understates the difficulty.
08 · What this scale proves
And what it does not prove.
Proves
- PDRN’s size is far beyond the conventional skin threshold.
- A human in vivo measurement has recorded low-rate penetration into the superficial viable epidermis.
- The process appears to be two steps: slow stratum corneum passage, then uptake-sensitive behaviour in the viable epidermis.
Does not prove
- That topical PDRN has no useful effect.
- That topical PDRN is interchangeable with a lower-strength injectable.
- That a 0.1% preparation of ≤850 kDa PDRN predicts the behaviour of the 435 products whose concentration cannot be determined.
The accurate wording is “enters the superficial epidermis at an extremely low rate — barely gets in, but not zero.”
Continue
Put the scale back into the argument.
Educational reference only. This site does not provide medical advice, treatment courses, injection counts, clinic recommendations or price recommendations.
PDRN is not approved by the FDA for injection or any therapeutic use. Topical and injectable PDRN are parallel facts under different regulatory pathways and must not be directly equated.
PN is not PDRN. Evidence grades are labelled on every factual element; in vitro and animal research is never described as clinical efficacy.