Would this also be beneficial in a topical?
Iāve 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)
1 Like
Iāve 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: yesāusing DEP (dermo-electroporation) will drive all components of that serum deeper than theyāre designed for. Most people will be fine, but the risk of stinging/irritation goes upāmainly from the solvents, humectant glycols, the PHA (gluconolactone), and the preservative/acid system. If youāre 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/edemaāusually 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 pointābut it also amplifies irritants.
- Common DEP contraindications (independent of the serum): pacemaker/implants, epilepsy, pregnancy/breastfeeding, active cancer, certain neuromuscular disorders. If any apply, donāt use DEP.
- Mattioliās own materials emphasize the methodās ability to move even large, ionized molecules (e.g., heparin) and state the system itself is generally non-irritatingāmeaning 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: 1ā2 pulses on a 2Ć2 cm area using diluted serum (e.g., 1:1 with sterile water or manufacturerās conductive solution). Wait 24ā48 h. Escalate only if no sting/erythema beyond 30ā60 min.
- Skip other actives that day (retinoids, AHAs/BHAs, vitamin C in low-pH forms). Youāre 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 reactionsāif anyāare transient.)
- Contraindications check before every session (implants, pregnancy, epilepsy, etc.). When in doubt, donāt.
Bottom line
- The formula is clean (no fragrances, no oils), but DEP will magnify the ābiteā 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.
3 Likes
The half-life of tadalafil is much better than sildenafil, so Iām going to try tadalafil first. It seems like the better option for the effect desired.
See:
Hereās the straight comparison ā itās one of the biggest pharmacokinetic differences between the two:
| Property | Tadalafil (Cialis) | Sildenafil (Viagra) |
|---|---|---|
| Half-life (tĀ½) | ~17.5 hours (range 15ā20 h) | ~4 hours (range 3ā5 h) |
| Onset of action | ~30ā45 minutes | ~30ā60 minutes |
| Duration of effect | Up to 36 hours (āthe weekend drugā) | 4ā6 hours |
| Metabolism | CYP3A4 ā catechol metabolite | CYP3A4 & CYP2C9 ā desmethyl-sildenafil |
| Active metabolites | None significant | One minor, ~50% potency |
| Steady-state (daily use) | Reached in 5 days | Rarely dosed daily due to short tĀ½ |
Key implications
- Tadalafilās ~17-hour half-life means more stable and sustained PDE5 inhibition ā smooth, prolonged vasodilation and endothelial nitric-oxide support.
- Sildenafil gives a stronger but shorter spike; its plasma levels drop rapidly after 6ā8 hours.
- For topical or transdermal formulations , tadalafilās 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 4ā5Ć longer-acting than sildenafil, both systemically and (likely) in dermal tissues if absorption is similar.
2 Likes
Yes, and I have non reactive skin but I am very careful to maintain its barrier ā which is, I believe, partly WHY it is so non reactive. It used to be more sensitive when I didnāt 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 wouldnāt 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 theyāre made in sterile packaging meant to be opened and used on the spot, without the ingredients I wouldnāt want past the skin barrier. Remember with sildenafil youāll also get more vasodilation and blood flow there, which means more of these molecules will be carried systemically.
3 Likes
Age related vascular degeneration in the skin is the reason many people develop venous leg ulcers, as in my fatherās 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 āgood qualityā, and why I started using Ketoscell with the tretinoin. Wish I had gotten 10 tubes of it in MX 
4 Likes
Iāve 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. Iām really looking forward to experimenting with this.
Iām 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 
1 Like
Interestingā¦ so you saw that overall as a negative on Tadalafil? I took that all as a positiveā¦ some systemic would be good (but typically using transcutol you are not going to get systemic exposure I suspect)ā¦ and the long half life would be good as you could use it once per day and get ongoing benefits.
Whatever, itās going to be interesting to try this.
2 Likes
The reason is that my supplier doesnāt have any at this time
But Iām not letting that get in my way and Iāve 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, thereās 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 Iād like to use this family of compounds every day and I donāt 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 itās 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 Iām just going to ease into it and not go too hard at it
1 Like
Just reviewing this thread and thinking of trying this soon. Noticed that this product is available from the regular Indian pharmacies very cheap - so may pick some upā¦ mix with tadalafil per the recipes mentioned in this thread.
2 Likes
Steve - did you ever play with this? any results you can report?
1 Like
My little hobby is sucking up all my time these days and Iāve not had much time to experiment with the fun things.
Iāve got some help in the lab now so Iām hoping next week I can get back at this project.
Iām going to do a serum for both scalp and general skin care.
It will contain,
Sildenafil
AHK-cu
TB4 aa43
Nicotinic Riboside (NR)
And a minimum of compounds it needs to be a serum.
I added NR to our topical lotion and it seems to be making a difference. As we age our pores get bigger, mine have been getting smaller the past 2 months since we added it as well as a reduction in very fine wrinkles under my eyes. Not much effect with creases or large wrinkles though.
I use this on my scalp as well and it seems to have slowed my hair loss, which was picking up steam in the past year. No restoration though.
This lotion has only 13 ingredients, with the 4 major players being,
GHK-cu 2%
Hyaluronic Acid ULMW 1.5%
NR 2%
Argan Oil 7%
Here is why I added NR to the topical and will add it to the serum for micro-needling and DEP
Rejuvenation_Creme_v3 - NR.pdf (92.9 KB)
3 Likes
Iāve been using my tadalafil skin cream for the past two weeks and I believe Iām seeing some improvement in color and tone of my skin, with a shift towards a more youthful āpinkā tint. But, its early ā¦ Iāll report more in another month when I have more of a longer period of use. Right now Iām using the cream every morning and evening (after washing my face). So far, no side effects.
On a slightly different tangent, I was doing more research on topical use of PDE5 inhibitors, and came across this paper, that may be of interest to people. I donāt have access to the full paper, but will try to get it from some of my academic sources when I have a chance (and will post it then).
Comparative study between the Efficacy of Topical Sildenafil 2% and Topical Minoxidil 5% in the Treatment of Male Androgenic Alopecia
Gemini 3 Pro Summary of paper:
Summary: Efficacy of Topical Sildenafil 2% vs. Topical Minoxidil 5% for Male Androgenic Alopecia
Publication: Al-Azhar International Medical Journal, April 2025 DOI: 10.21608/aimj.2025.446532 Clinical Trial Registration: NCT05369481
Overview and Rationale
Androgenetic alopecia (AGA) is characterized by follicular miniaturization driven by systemic androgens and genetic factors. While topical minoxidil 5% is the FDA-approved standard, adherence is often compromised by application-site side effects (e.g., scalp irritation, pruritus, scaling) and an initial shedding phase.
Sildenafil, a selective phosphodiesterase type 5 (PDE5) inhibitor, was investigated as an alternative. Its proposed mechanism for hair growth relies on its vasodilatory properties, enhancement of human dermal papilla cell proliferation, and the localized upregulation of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).
Methodology
The study was an interventional, randomized, parallel-assignment clinical trial. Male subjects (aged 18ā45) with clinically diagnosed AGA were divided into two treatment arms:
- Experimental Group 1: Applied topical Sildenafil 2% twice daily for six months.
- Experimental Group 2: Applied topical Minoxidil 5% twice daily for six months.
Efficacy was evaluated using trichoscopy to quantify terminal hair count, vellus hair count, and hair thickness across specific scalp regions. Secondary outcomes included global photographic assessments, patient self-assessment questionnaires, and tracked side-effect profiles.
Key Findings
- Efficacy: Both interventions yielded a statistically significant increase in terminal hair count, hair thickness, and overall hair density from baseline after the six-month treatment period.
- Patient Satisfaction: There was no statistically significant difference in subjective patient satisfaction scores between the topical sildenafil 2% group and the topical minoxidil 5% group. Both cohorts reported comparable perceived clinical improvement.
- Tolerability: The incidence and severity of side effects were not significantly different between the two treatment groups.
Actionable Insights and Systemic Implications
- Alternative Pathway: Sildenafil 2% provides a viable, non-hormonal treatment alternative for male AGA. By inhibiting PDE5 and upregulating VEGF/PDGF, it acts via a distinct mechanism from minoxidil (a potassium channel opener) or finasteride (a 5-alpha-reductase inhibitor). This makes it a functional substitute for individuals who exhibit poor tolerance to minoxidilās vehicle or experience adverse reactions.
- Microvascular Health: The demonstrated efficacy of a localized vasodilator in reversing AGA highlights the critical role of microvascular circulation and endothelial health in tissue maintenance and cellular regenerationāa central focus in actionable longevity protocols. Interventions that preserve vascular integrity often yield compounded downstream benefits for tissue longevity.
Knowledge Gaps and Required Data
- Long-Term Efficacy: AGA interventions require indefinite application to prevent regression. A six-month trial is insufficient to determine if sildenafil 2% maintains anagen (growth phase) induction long-term, or if physiological tachyphylaxis reduces its efficacy over consecutive years.
- Synergistic Potential: The study evaluates these compounds as monotherapies. Additional clinical trials are needed to ascertain if the co-administration of topical sildenafil 2% and minoxidil 5% yields additive or synergistic effects, given their overlapping but distinct mechanisms of action.
- Statistical Power: Full evaluation of the studyās statistical power, exact cohort attrition rates, and precise demographic variances are necessary to verify the absolute non-inferiority of sildenafil relative to minoxidil across diverse genetic backgrounds.
1 Like