Would this also be beneficial in a topical?
Iâve been considering adding NMN or NR to one of my skin care experiments.
They may also compliment sildenafil or Tadalafil as I noticed in one of the post nicotinamide mentioned.
NMN or NR for topical use.pdf (223.3 KB)
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Iâve been using the DEP machine with regular topical serums with no issues, so it seems ok so far.
Also, I took the ingredients list from one of the products and ran it by CGPT5, and here is what it said:
Short answer: yesâusing DEP (dermo-electroporation) will drive all components of that serum deeper than theyâre designed for. Most people will be fine, but the risk of stinging/irritation goes upâmainly from the solvents, humectant glycols, the PHA (gluconolactone), and the preservative/acid system. If youâre going to pair them, do it conservatively.
Where the risks come from (ingredient-by-ingredient)
- Ethoxydiglycol (solvent/penetration enhancer): generally low irritancy, but higher concentrations can dry/irritate skin; DEP will further increase penetration.
- Propanediol & Pentylene glycol (humectant solvents): typically mild, but can sting on compromised skin; DEP can amplify that by shuttling more into viable epidermis. (General irritation data for these glycols is mild but formulation-dependent.)
- Gluconolactone (PHA): usually gentle, but still an acid; electroporation increases permeation of actives, so expect a higher chance of transient burning/erythema.
- Citric acid / Sodium citrate (pH control): acidity contributes to sting; deeper delivery magnifies that sensation. (Mechanism: EP transiently disrupts stratum corneum to let ions/solutes through.)
- Sodium benzoate (preservative): generally safe at cosmetic levels, but EP raises benzoate flux across skin; stinging risk increases, especially at lower pH.
- Hyaluronic acid / Sodium hyaluronate, Glycerin, Water: low intrinsic irritancy; HA/glycerin are humectants. With DEP you might see transient plumping/edemaâusually benign. (Mechanism: DEP drives water-soluble compounds several mm into skin.)
Device-side factors that matter more with this pairing
- DEP increases transdermal flux of small and large molecules by creating transient aqueous pathways; this is the whole pointâbut it also amplifies irritants.
- Common DEP contraindications (independent of the serum): pacemaker/implants, epilepsy, pregnancy/breastfeeding, active cancer, certain neuromuscular disorders. If any apply, donât use DEP.
- Mattioliâs own materials emphasize the methodâs ability to move even large, ionized molecules (e.g., heparin) and state the system itself is generally non-irritatingâmeaning any reaction is more likely from what you push through, not the pulses.
Practical way to use them together (if you insist)
- Patch test with DEP: 1â2 pulses on a 2Ă2 cm area using diluted serum (e.g., 1:1 with sterile water or manufacturerâs conductive solution). Wait 24â48 h. Escalate only if no sting/erythema beyond 30â60 min.
- Skip other actives that day (retinoids, AHAs/BHAs, vitamin C in low-pH forms). Youâre already boosting penetration.
- Keep sessions short, spacing wider (e.g., weekly), then step up based on tolerance. DEP can deliver much larger volumes quickly, so err on the low side.
- Mind the barrier: if you feel sharp sting that persists >60 min, or see patchy erythema/itch, stop and revert to bland emollients until fully calm. (Most reactionsâif anyâare transient.)
- Contraindications check before every session (implants, pregnancy, epilepsy, etc.). When in doubt, donât.
Bottom line
- The formula is clean (no fragrances, no oils), but DEP will magnify the âbiteâ of its acid system (gluconolactone/citric) and solvents (ethoxydiglycol, propanediol, pentylene glycol) .
- Expect a moderate irritation risk with DEP compared to low risk when applied conventionally.
- If you want fewer variables, use a DEP-approved conductive HA solution or dilute this serum for DEP days and reserve the full-strength serum for non-device use.
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The half-life of tadalafil is much better than sildenafil, so Iâm going to try tadalafil first. It seems like the better option for the effect desired.
See:
Hereâs the straight comparison â itâs one of the biggest pharmacokinetic differences between the two:
| Property | Tadalafil (Cialis) | Sildenafil (Viagra) |
|---|---|---|
| Half-life (t½) | ~17.5 hours (range 15â20 h) | ~4 hours (range 3â5 h) |
| Onset of action | ~30â45 minutes | ~30â60 minutes |
| Duration of effect | Up to 36 hours (âthe weekend drugâ) | 4â6 hours |
| Metabolism | CYP3A4 â catechol metabolite | CYP3A4 & CYP2C9 â desmethyl-sildenafil |
| Active metabolites | None significant | One minor, ~50% potency |
| Steady-state (daily use) | Reached in 5 days | Rarely dosed daily due to short t½ |
Key implications
- Tadalafilâs ~17-hour half-life means more stable and sustained PDE5 inhibition â smooth, prolonged vasodilation and endothelial nitric-oxide support.
- Sildenafil gives a stronger but shorter spike; its plasma levels drop rapidly after 6â8 hours.
- For topical or transdermal formulations , tadalafilâs long half-life is a double-edged sword :
-
Pros: longer local effect, less frequent dosing. -
Cons: more risk of cumulative low-level systemic exposure if applied over large areas daily.
-
So tadalafil is roughly 4â5Ă longer-acting than sildenafil, both systemically and (likely) in dermal tissues if absorption is similar.
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Yes, and I have non reactive skin but I am very careful to maintain its barrier â which is, I believe, partly WHY it is so non reactive. It used to be more sensitive when I didnât know how to care for it and when I used a ton of topicals with such irritants as listed there (minus the HA / glycerol which are good). So personally I wouldnât use it with serums meant for topical application because they include such ingredients as were needed for shelf stability and to keep it bacteriostatic or enhance penetration but which only make sense, if at all, for topical application. You might get no adverse effects immediately but over time you might see more sensitive skin, more acne, more rashes etc. Not worth it to me. I stick with those skin boosters because theyâre made in sterile packaging meant to be opened and used on the spot, without the ingredients I wouldnât want past the skin barrier. Remember with sildenafil youâll also get more vasodilation and blood flow there, which means more of these molecules will be carried systemically.
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Age related vascular degeneration in the skin is the reason many people develop venous leg ulcers, as in my fatherâs case. Skin health is not just about aesthetics and should not be underestimated. Topical tadalafil and other interventions mentioned here seem like effective, doable solutions. I recently discovered that topical pirfenidone, sold as Ketoscell, reverses the fibrotic mechanisms which play a role in skin aging. This shift to fibrosis is the reason why collagen production in aging skin is not âgood qualityâ, and why I started using Ketoscell with the tretinoin. Wish I had gotten 10 tubes of it in MX 
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Iâve put the Tadada order on hold but have the Sildenafil pharma grade bulk powder (>98%) on its way, should be here in 3 to 4 weeks. Iâm really looking forward to experimenting with this.
Iâm also going to elevate it at some point with BPC 157 + Thymosin Beta 4 + GHK-cu for additional local benefits related to VEGF, NO production and some of the other benefits, and maybe KPV to further reduce local inflammation.
Next step before it arrives is to get our AI friends to make a skin safe gell formula for micro needing and electroporation. The DEP machine should be here before the Sil 
Interesting⌠so you saw that overall as a negative on Tadalafil? I took that all as a positive⌠some systemic would be good (but typically using transcutol you are not going to get systemic exposure I suspect)⌠and the long half life would be good as you could use it once per day and get ongoing benefits.
Whatever, itâs going to be interesting to try this.
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The reason is that my supplier doesnât have any at this time
But Iâm not letting that get in my way and Iâve considered the following.
There is a LOT of skin to cover, I want it all to be healthy not just the visible parts like face and neck, thereâs hands, arms, chest, legs, feet. So applying a long lasting compound like Tada may not be the best answer for whole body use??
With Tadalafils half life of 17hr it may have the advantage of a once or twice weekly application. But Iâd like to use this family of compounds every day and I donât think that would be judicious.as it will be in the system for an extended period of time, up to 3-4 days for total elimination, with diminishing effects of course.
Sildenafil with itâs shorter half life of 3 - 5 hr can be used every day as a topical with little concern about increasing the amount in your system as it is completely eliminated in 16 to 24hr. I can then target more of the skin area without too much concern about having too much in my system over a longer period of time.
I do plan to use these with a combination of micro needling and electroporation once a week with basic topical applications in between.
So Iâm just going to ease into it and not go too hard at it
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