Hypothesis Topical Thiazolidinediones (volufiline that ACTUALLY WORKS⁉️) (GTFIHHH)

[giga.mia]

nice thread neegy. do you know how to make lobeglitazone? is it a similar formula to rosi.

It would ideally be the same as the formula for rosi I’m working on

 

[Jack-O'-Lantern]

I’m sure everyone here has heard of volufiline, or other topicals that are marketed to give a lipofilling effect. Go check out @genio thread eviscerating volucope

Guide Volufiline: Why it's Cope and What to Do Instead

Jul 2, 2026

Volufiline: Why it's Cope and What to...​

• genio
• Replies: 40
• Forum: Looksmaxxing

• 
• 
• 

His thread mentions Rosiglitazone under non surgical procedures, which is something that’s garnered a bit of attention from this community. Rosiglitazoney is a potent PPAR-γ agonist belonging to the drug class of thiazolidiones, and it is a hidden gem for localized fat growth. I mean that literally. It was a potential product that was buried.


Mechanism

View attachment 388571

I’m sure most of us are familiar with what type 2 diabetes is. When your bodies insulin receptors become desensitized, making it harder to store energy appropriately. Because of this, people with type 2 often have higher levels of insulin since their body is trying to fight their resistance. But this obviously doesn’t last them forever, and stresses the beta cells in their pancreas to death. Well oral TZDs (Thiazolidinediones), like rosiglitazone and pioglitazone aim to work around this issue by targeting the PPAR-γ receptor (peroxisome proliferator-activated receptor gamma) which sits in the nucleus inside the cells. It indirectly helps with clearing the bloodstream of glucose/storing it, adipogenesis, and insulin sensitivity. To be more specific, when the receptor is activated, it binds and creates a heterodimer with RXR to transcribe genes.
Its change in gene expression causes more GLUT4 production which is the transporter that allows glucose to enter the cell. Hence, higher insulin sensitivity and less blood sugar. It also promotes differentiation of preadipocytes into mature adipocytes. Rosiglitazone (Avandia) is administered with a starting dose of 4mg, but if patients respond inadequately follow 8-12 weeks of treatment they can bump their dosage up to 8mg.

We don’t have tons of clinical studies conducting research on applying this in topical form onto humans, since it was created as a diabetes medication. But there are still studies about its topical use here and there that suggest its healing properties:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12023181/
https://pmc.ncbi.nlm.nih.gov/articles/PMC3733781/
https://www.cell.com/molecular-therapy-family/advances/fulltext/S3117-387X(26)00067-4
https://www.sciencedirect.com/science/article/pii/S0022202X15371050

Rosiglitazone and pioglitazone are the two main thiazolidiones that have been investigated as topicals. But there are still plenty of others under that drug class that have been researched but less extensively (ex: ciglitazone, troglitazone).

Risks
Let’s talk about practically EVERY SINGLE risk related to TZDs. Let’s keep in mind that most of these risks are minimized in the form of topical use.

1. Edema. If you’re unaware of what this is, it’s the medical term for swelling from excess fluids being trapped in your bodies tissues. The PPAR-γ receptor is not only present in regular adipocytes but it is also in kidney cells, particularly in the collecting ducts and distal tubules. The goal of the DSCT is to reabsorb more sodium chloride and water. The hormones aldosterone and ADH can act upon this. ADH will talk to dct increase water reabsorption , aldosterone will increase salt reabsorption. So remaining sodium winds up in the collecting duct to be reabsorbed. I’ll remind you of the inverse relationship between sodium and potassium- sodium pulls fluid outside of cells while potassium stores it inside. Activation of the PPAR-γ receptor causes more sodium reabsorption back into the bloodstream, and since water moves by osmosis more water is also reabsorbed. This causes a big bloated mess, and the fluid leaks into surrounding tissues. It’s specifically called peripheral edema, but there’s also other kinds of edema that have been reported. Macular edema is swelling in the macula, causing vision changes. Some of you might be aware of the fact that this has been reported before as a rare adverse affect from TZDs. But we have to keep in mind that people who have blood retinal barrier dysfunction (from their diabetes) are the ones who are at higher risk of this. Having diabetes alone usually causes a certain degree of damage to that barrier, so in most reports it’s very possible that the TZD just exacerbated a pre existing issue, and I think most of us on here are NOT diabetic. Most of the reports of macular edema even wind up being reversible, so their vision goes back to normal after stopping. This is because edema is only fluid buildup, it’s not necessarily causing permanent damage to the surrounding cells, it’s just disarranging them out of place. Now how do we work around this..? Well we’re gonna be making a TOPICAL formulation. Meaning it’s only going to work locally. If you look at all of these cases of edema, it’s from diabetics who frequently take oral TZDs as well as usually taking insulin alongside it.
2. Heart problems. If you read what I said for edema, it’s practically the same cause. The body starts to gain more fluid retention since more sodium and water get reabsorbed back into the bloodstream. More fluid starts to circulate through your bloodstream, so because of that your heart will have a heavier preload. It will have to pump a larger volume of blood. That’s why TZDs can worsen a heart that’s already weakened, or even cause new problems since overload that’s very prolonged (months to years) will stress your heart. Now how would we work around this? Well we wouldn’t even have to. A topical formation isn’t gonna give you heart failure as it only works locally
3. Increased cholesterol. Both rosiglitazone and pioglitazone lower triglycerides and increase HDL levels..but apparently rosiglitazone can increase LDL, and so can pioglitazone but to lower extents. If your body builds up too much of the bad cholesterol, it builds up in the walls of your arteries. Causing dangerous plaque to form, which narrows the artery. It can build up in very important arteries that supply blood flow to the heart and even the brain.
4. Hypertension. This is just more of the same stuff. Hypertension is the word for chronically high blood pressure, which can damage your heart and kidneys. Because of the fact that oral TZDs can cause more water and sodium reabsorption into the circulation, your blood volume will increase.
5. Hypoglycemia. This actually rarely happens when only on TZDs, but hypoglycemia is when your blood glucose levels are too low. After activating the PPAR-γ receptor, your cells will become more responsive towards insulin. Sometimes this piece alone is enough to knock someone’s blood sugar levels too low.
6. Bladder cancer. This appears as an adverse effect more specifically from pioglitazone. It’s a proposal that stemmed from studies on male rats, but human studies show little to no correlation. This possible correlation, however, is thought to be from long term exposure. From your bladder cells being repeatedly exposed to the pioglitazone metabolites.
7. Bone fracture. The stem cells inside bone marrow can either become adipocytes or osteoblasts. By activation of the PPAR-γ receptor you probably understand which kind of cell is chosen. Overtime if your body starts disproportionally making more marrow adipocytes at the expense of osteoblasts, your bones will weaken. Older women in particular are at the highest risk of this adverse effect.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5651605/

Now if you look at all of these adverse affects, you can clearly see that practically ALL of these are from oral intake. I don’t think applying a topical formulation of one of these TZDs is gonna travel all the way to your kidneys…fuck up your sodium excretion…travel to your retina…blind you permanently..so on and so forth.

The idea of topical TZDs is so convenient, that’s it’s literally been experimented with in the past. Meet Topokine Therepeutics. This biotech company experimented with creating topical rosiglitazone and other tzds in the past, as a product for local fat optimization.

https://patentimages.storage.googleapis.com/54/17/e8/fe6c9c5256bbc3/US8883834.pdf?utm

This document outlines their project. On page 33 you can see the results of the experiments they conducted. They experimented with creating formulations with different kinds of thiazolidinediones, including formulations containing 0.1% and 0.3% rosiglitazone. Incredible results were revealed.

In order to create a topical formulation for this, it’s important that it reaches the subcutaneous layer without being systemically absorbed through your bloodstream. That’s probably the main reason why the project was abandoned, the critics of it didn’t think the public would respond nicely to this idea of using a diabetes medication topically. Because of the network of capillaries in the skin's dermis. Topokine Therapeutics addressed this as the “sink condition”.

View attachment 388582

It’s a pharmacological term describing how specific tissues act as “sinks”, transporting the medication into the bloodstream instead of the target site. This is a prevalent effect in subcutaneous drug delivery, let alone pharmacokinetics in general.

Drug molecules will naturally move from high concentration to low concentration, so the capillaries in the dermis offer a lower concentration for the molecules to gravitate towards, which eventually lead to them entering your bloodstream. Thiazolidinediones are lipophilic, so they are literally in favor of penetrating deeply and reaching the bloodstream. They aimed to make something that could penetrate the skin enough to enter the subq layer, but WITHOUT diffusion into the capillaries.

View attachment 388583

What’s so damn splendid about their creation is how it somehow counters the sink effect. Somehow implanting the medication into the subq layer with negligible amounts of systemic exposure. The patents proved this by running multiple drug tests including Cmax, AUC, LC-MS/MS. They collected blood samples from all of the pigs they tested on. They concluded that peak plasma concentrations were about 3400 and 1300 FOLD LOWER than for oral therapy. Over the 42 day dosing period only that smidgen made it into the bloodstream.

It’s unclear how the ingredients work together to deliver the drug into the fat layer with minimal systemic exposure. But I think I figured out the mental gymnastics. If you zoom into the molecular picture, rosiglitazone is ~357 Da. According to the Dalton rule this can easily penetrate the skin barrier, and you would think with a weight like this it could easily get swelled up by the capillaries. But the ingredients all work together to swarm down the skin barrier so fast the capillary network doesn’t even see them coming. The ethanol evaporates onto your skin whilst altering the stratum corneum. After this layer is left behind, the concentrations of the other ingredients skyrocket since over 65% of the product has dissipated. The remaining propylene glycol can barely hold the drug so the liquid becomes supersaturated. The drug gets blasted through the loose dermis. The capillaries in the skin are not fenestrated. They’re continuous, and once the drug molecules reach these capillaries they ambush the microscopic transport pores. The idle lipophilic molecules immediately passively diffuse into the subcutaneous layer beneath the dermis, and they stay there.

After 42 days of using 0.3mL on 6 different treatment areas, a mean of a whopping 48% fat increase was noticed. Four mini pigs (the animal with the most similar skin to humans) were tested on.

View attachment 388584

I’m gonna shout this again. The mean fat thickness over placebo is a 48% INCREASE.

Now for the million dollar question, what’s the recipe for this topical formulation that they used?

View attachment 388585

Each one of these ingredients (aside from our tzd) are fundamentally safe for topical human use and are common ingredients in the skincare industry.

You can substitute the rosiglitazone with other thiazolidiones like pioglitazone and experiment around, but if you take the time to read the patents papers, pioglitazone in particular doesn’t give the most outstanding results. It still worked, but not as well as rosiglitazone. There’s other glitazones as well like ciglitazone. Lobeglitazone is the one that’s even stronger than rosiglitazone, and patients only take 0.5 mg of it. There’s just so many others under this drug class that people could experiment with.

Formulation ingredients:
Rosiglitazone
This is the TZD we’d be using, the patent is never actually clear on what form of rosiglitazone they used. But according to the context clues I’d say that the experiment did NOT use the malleate version (rosiglitazone malleate is the kind they use in the oral tablets), and they probably just used regular free base rosiglitazone. If they had used any specific version they would have specified. Looks like you can find rosiglitazone on this marketplace, but make SURE what you get is in free base form. https://www.echemi.com/searchGoods/temppid160705010001-rosiglitazone.html
https://www.glentham.com/en/products/product/GP6434/?utm_
https://www.chemimpex.com/products/...-8Kb6Rnp20YfaLU3IthxlarNo-QtVinjNxU4rMzQ9sfzi

Alpha-tocopherol (aka vitamin E)
is an antioxidant so that the gel doesn’t go bad. It’s unclear whether they used synthetic or natural in their experiments..but they do list exemplary antioxidants that are synthetic so I don’t think it matters. I found this gem for cheap, and it’s pure free tocopherol. You only need a very miniscule amount of this for it to do its job. Pure dl-alpha-tocopherol has a density of roughly 0.95 grams per milliliter, so you’d only need .0021ml of this stuff in the 100g formulation. Now because of the fact that that’s practically fucking impossible to measure, you’re gonna do the stock solution method to measure it (I’ll elaborate in the “how to” section)
https://www.makingcosmetics.com/VIT-VITE-01.html?lang=en_US

Anhydrous ethanol (ethanol with practically no water)
will help the product penetrate the stratum corneum as I said before. The kind they used was very pure, look for 200 proof non denatured ethanol. You’d use about 86.3mL of this per 100g of final product.
https://www.usalab.com/usa-lab-200-proof-ethanol-usp-99-97-1gal-5gal-55gal-270gal-excise-tax-included/?

As for the propylene glycol, you want very pure medical grade product asw. You’d add 26.06ml of this into the 100g batch.
https://www.walmart.com/ip/Propylen...-non-gmo-premium-natural-pure-32-oz/829649994

3.37ml of oleic acid in 100g batch
https://www.ebay.com/itm/2222473408...gdN5wKS3mgfbW8c4gSl0xzSvG3jSWrInknpDTQZPmDL-o

For the Klucel/HPC,
they don’t specify what grade they used. But from context clues, they most likely used Klucel® HF. (Edit: I don’t know why the fuck I said context clues, it literally says HF.) The formulation is supposed to be a gel, and if you added only 1g of something like EF/LF in a 10g batch, that would barely change the consistency at all. This should be weighed on a scale (favorably a four place balance, but that’s pretty expensive shit that I wouldn’t assume many of you have. A three place balance is aight instead)

https://www.kremer-pigmente.com/en/shop/mediums-binders-glues/63713-klucel-hf-pharm.html

Spoiler: How you’d actually cook this up

You’re going to want one syringe per ingredient. Cross contamination is a no no, getting everything precise is crucial. Get a nice big pack of syringes. https://www.ebay.com/itm/387000288770

https://www.premiumvials.com/30-pac...Qp_gX7QNZmwUChkbjH3VwgjSt4VcmSh_YAsvW342vvcDy

For this mixture, an amber glass mason jar works well. Since amber glass absorbs all kinds of light wavelengths. Keep that lid next to you at all times. Your mixture needs minimal exposure to air.
https://www.premiumvials.com/2-oz-a...127&gbraid=0AAAAADpaBkCcgWGovPzMQy67RBWzvL57P

Wear a mask when handling the rosiglitazone powder. You don’t want to inhale it.

The anhydrous ethanol is an ingredient you shouldn’t fuck around with, it should have MINIMAL exposure to air. The air will ruin it. The ethanol is so pure so if left exposed for the air for too long it can absorb water from the air, which fucks up your ratios and the entire point of it being “anhydrous”. Never ever leave the cap off of your ethanol bottle, it will spoil the whole thing.

And it just so happens to be the first product topokine therepeutics adds to the batch. So you should draw up all your other liquid ingredients beforehand so this entire mixing process goes as fast as possible.

You need only 2.1 µL of vitamin E. In order to measure this, you’re gonna make a 1:100 stock solution including propylene glycol. Add 9.9ml of propylene glycol and 0.1ml of vitamin e in a small vial. Now every 1 ml of the liquid has 0.01ml of vitamin E. You’d deduct 0.21ml of this stock solution with a syringe to get .0021ml of vitamin E.

Now because most of that stock solution is propylene glycol, you’re just gonna subtract that amount from your main batch to be precise and avoid any mishaps in your ratios. So you’d go 26.06ml - 0.21ml for your main propylene glycol measurement.

The first ingredient to add to the solvent beaker is 86.3ml of Anhydrous ethanol. Then after that, you’d immediately add your 25.85ml of propylene glycol, 3.37ml of oleic acid, and 0.21ml of stock solution (the vitamin E). Immediately cover your batch with the lid after adding all these. Also IMMEDIATELY put the caps back on the bottles of your chemicals, ESPECIALLY the ethanol.

Now it’s time for you to weigh out the powders. You can take your time for this part since your mixture is covered.

What sucks is you’d ideally want to use a 4 place balance to measure these out, but not a single one of those is under 100 bucks. So a cheaper 3 place scale is usually where you end up. When weighing these out, the scale should be far away from any vents, windows, fans, or anything that could possibly mess with it. Zero the scale out and you can put some weighing paper on it for the powder. Then scoop some tiny amounts of the rosiglitazone powder onto the scale. When the scale finally reads 1g, carefully funnel the weighing paper and add the powder to the batch. Stir until the liquid is clear, and then cover it back up again.

Now for the Klucel, you’re gonna weigh out 1g of it the same way you did rosiglitazone. Go over to the scale and weigh 1g. It has a relatively low bulk density, so don’t be surprised if 1g looks bulkier than it should. Dispersing this powder is incredibly important, as this is the ingredient that gives your gel its viscosity. You’re gonna uncover your batch and start whisking that shit away with a stirring rod like there’s no tomorrow. While you stir your mixture in this volatile manner, sprinkle in the Klucel. You want to scatter each dry particle of the powder throughout your mixture. Once the Klucel is all the way sprinkled in, SLOW your stirring speed to avoid bubbles. This entire dispursement should be 1-2 minutes, after that cover your shit up immediately. Remember, ethanol is a ticking time bomb.

Now, you let your batch sit. Store it in a dark cabinet away from any light (thiazolidiones are light sensitive). After 2 hours you can take it out, take the lid off and stir it for another minute. This will be the final time you stir it for the day. Then put it back and let it sit overnight.

The next day, you can begin to use your gel. It shouldn’t look cloudy/grainy, but instead uniform and smooth.

It should be stored long term in a pitch black pantry/cabinet, at a stable room temp.
View attachment 388600

Potential flaw/s: I’m sure when most of us think of volufiline, we think of something to fill recessed infras. A potential flaw with that is that the skin around the eyes is the part of the body with the thinnest skin. With how well the topical gel works, its permeability is what should make you feel weary about applying it there. A viable workaround for this would be to create an alternative formulation with less penetration enhancers.

You wouldn’t want this gel to touch your actual lower eyelid either (aegyo sal), or else you’d be giving yourself steatoblepharon. Applying a pea sized amount of the gel and rubbing it in your desired areas whilst putting tape on your lower eyelid (to ensure the gel doesn’t touch it), would be the safer way to go. Not risk free though. However applying this gel to your under eyelid is not going to wind up in the retina (causing muh macular edema). The capillaries under your eyelid don’t flow backwards towards the retina, they take blood away from the eye. What supplies the retina is the central retinal artery, which is way in the back of your eyeball in the optic nerve trunk. The actual risks here concerning applying this to the infras would be a possible increased amount of the drug in your bloodstream (from the network of ocular capillaries close to the surface of the thin skin), and the product working too well in the wrong places.

Applying it to the supras on the other hand is safer (the skin is thicker there), but you’d have to be very careful about the gel migrating or touching your actual upper eyelid. You wouldn’t want to be thickening your actual eyelid, you’d be giving yourself ptosis. A work around to this would be applying the gel right on your eyebrow, and putting tape on your eyelids just in case.

This is all hypothetical I’m not a professional don’t sue me
@Mandy? @ecoli @Histy @LaWi @Arya @Whitepill @foidslayer

formatting of doom and despair

 

[giga.mia]

formatting of doom and despair

Literally how

 

[Jack-O'-Lantern]

Literally how

pink

 

[giga.mia]

pink

Stupid boy doesn’t like the best color!

 

[Jack-O'-Lantern]

Stupid boy doesn’t like the best color!

I like black

 

[giga.mia]

I like black

Did you know you can like multiple colors

 

[Jack-O'-Lantern]

Did you know you can like multiple colors

yeah
I like light pink, the cream kind, or like, vagina pink or whatever it's caled

 

[humbleMTN]

I’m sure everyone here has heard of volufiline, or other topicals that are marketed to give a lipofilling effect. Go check out @genio thread eviscerating volucope

Guide Volufiline: Why it's Cope and What to Do Instead

Jul 2, 2026

Volufiline: Why it's Cope and What to...​

• genio
• Replies: 40
• Forum: Looksmaxxing

• 
• 
• 

His thread mentions Rosiglitazone under non surgical procedures, which is something that’s garnered a bit of attention from this community. Rosiglitazoney is a potent PPAR-γ agonist belonging to the drug class of thiazolidiones, and it is a hidden gem for localized fat growth. I mean that literally. It was a potential product that was buried.


Mechanism

View attachment 388571

I’m sure most of us are familiar with what type 2 diabetes is. When your bodies insulin receptors become desensitized, making it harder to store energy appropriately. Because of this, people with type 2 often have higher levels of insulin since their body is trying to fight their resistance. But this obviously doesn’t last them forever, and stresses the beta cells in their pancreas to death. Well oral TZDs (Thiazolidinediones), like rosiglitazone and pioglitazone aim to work around this issue by targeting the PPAR-γ receptor (peroxisome proliferator-activated receptor gamma) which sits in the nucleus inside the cells. It indirectly helps with clearing the bloodstream of glucose/storing it, adipogenesis, and insulin sensitivity. To be more specific, when the receptor is activated, it binds and creates a heterodimer with RXR to transcribe genes.
Its change in gene expression causes more GLUT4 production which is the transporter that allows glucose to enter the cell. Hence, higher insulin sensitivity and less blood sugar. It also promotes differentiation of preadipocytes into mature adipocytes. Rosiglitazone (Avandia) is administered with a starting dose of 4mg, but if patients respond inadequately follow 8-12 weeks of treatment they can bump their dosage up to 8mg.

We don’t have tons of clinical studies conducting research on applying this in topical form onto humans, since it was created as a diabetes medication. But there are still studies about its topical use here and there that suggest its healing properties:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12023181/
https://pmc.ncbi.nlm.nih.gov/articles/PMC3733781/
https://www.cell.com/molecular-therapy-family/advances/fulltext/S3117-387X(26)00067-4
https://www.sciencedirect.com/science/article/pii/S0022202X15371050

Rosiglitazone and pioglitazone are the two main thiazolidiones that have been investigated as topicals. But there are still plenty of others under that drug class that have been researched but less extensively (ex: ciglitazone, troglitazone).

Risks
Let’s talk about practically EVERY SINGLE risk related to TZDs. Let’s keep in mind that most of these risks are minimized in the form of topical use.

1. Edema. If you’re unaware of what this is, it’s the medical term for swelling from excess fluids being trapped in your bodies tissues. The PPAR-γ receptor is not only present in regular adipocytes but it is also in kidney cells, particularly in the collecting ducts and distal tubules. The goal of the DSCT is to reabsorb more sodium chloride and water. The hormones aldosterone and ADH can act upon this. ADH will talk to dct increase water reabsorption , aldosterone will increase salt reabsorption. So remaining sodium winds up in the collecting duct to be reabsorbed. I’ll remind you of the inverse relationship between sodium and potassium- sodium pulls fluid outside of cells while potassium stores it inside. Activation of the PPAR-γ receptor causes more sodium reabsorption back into the bloodstream, and since water moves by osmosis more water is also reabsorbed. This causes a big bloated mess, and the fluid leaks into surrounding tissues. It’s specifically called peripheral edema, but there’s also other kinds of edema that have been reported. Macular edema is swelling in the macula, causing vision changes. Some of you might be aware of the fact that this has been reported before as a rare adverse affect from TZDs. But we have to keep in mind that people who have blood retinal barrier dysfunction (from their diabetes) are the ones who are at higher risk of this. Having diabetes alone usually causes a certain degree of damage to that barrier, so in most reports it’s very possible that the TZD just exacerbated a pre existing issue, and I think most of us on here are NOT diabetic. Most of the reports of macular edema even wind up being reversible, so their vision goes back to normal after stopping. This is because edema is only fluid buildup, it’s not necessarily causing permanent damage to the surrounding cells, it’s just disarranging them out of place. Now how do we work around this..? Well we’re gonna be making a TOPICAL formulation. Meaning it’s only going to work locally. If you look at all of these cases of edema, it’s from diabetics who frequently take oral TZDs as well as usually taking insulin alongside it.
2. Heart problems. If you read what I said for edema, it’s practically the same cause. The body starts to gain more fluid retention since more sodium and water get reabsorbed back into the bloodstream. More fluid starts to circulate through your bloodstream, so because of that your heart will have a heavier preload. It will have to pump a larger volume of blood. That’s why TZDs can worsen a heart that’s already weakened, or even cause new problems since overload that’s very prolonged (months to years) will stress your heart. Now how would we work around this? Well we wouldn’t even have to. A topical formation isn’t gonna give you heart failure as it only works locally
3. Increased cholesterol. Both rosiglitazone and pioglitazone lower triglycerides and increase HDL levels..but apparently rosiglitazone can increase LDL, and so can pioglitazone but to lower extents. If your body builds up too much of the bad cholesterol, it builds up in the walls of your arteries. Causing dangerous plaque to form, which narrows the artery. It can build up in very important arteries that supply blood flow to the heart and even the brain.
4. Hypertension. This is just more of the same stuff. Hypertension is the word for chronically high blood pressure, which can damage your heart and kidneys. Because of the fact that oral TZDs can cause more water and sodium reabsorption into the circulation, your blood volume will increase.
5. Hypoglycemia. This actually rarely happens when only on TZDs, but hypoglycemia is when your blood glucose levels are too low. After activating the PPAR-γ receptor, your cells will become more responsive towards insulin. Sometimes this piece alone is enough to knock someone’s blood sugar levels too low.
6. Bladder cancer. This appears as an adverse effect more specifically from pioglitazone. It’s a proposal that stemmed from studies on male rats, but human studies show little to no correlation. This possible correlation, however, is thought to be from long term exposure. From your bladder cells being repeatedly exposed to the pioglitazone metabolites.
7. Bone fracture. The stem cells inside bone marrow can either become adipocytes or osteoblasts. By activation of the PPAR-γ receptor you probably understand which kind of cell is chosen. Overtime if your body starts disproportionally making more marrow adipocytes at the expense of osteoblasts, your bones will weaken. Older women in particular are at the highest risk of this adverse effect.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5651605/

Now if you look at all of these adverse affects, you can clearly see that practically ALL of these are from oral intake. I don’t think applying a topical formulation of one of these TZDs is gonna travel all the way to your kidneys…fuck up your sodium excretion…travel to your retina…blind you permanently..so on and so forth.

The idea of topical TZDs is so convenient, that’s it’s literally been experimented with in the past. Meet Topokine Therepeutics. This biotech company experimented with creating topical rosiglitazone and other tzds in the past, as a product for local fat optimization.

https://patentimages.storage.googleapis.com/54/17/e8/fe6c9c5256bbc3/US8883834.pdf?utm

This document outlines their project. On page 33 you can see the results of the experiments they conducted. They experimented with creating formulations with different kinds of thiazolidinediones, including formulations containing 0.1% and 0.3% rosiglitazone. Incredible results were revealed.

In order to create a topical formulation for this, it’s important that it reaches the subcutaneous layer without being systemically absorbed through your bloodstream. That’s probably the main reason why the project was abandoned, the critics of it didn’t think the public would respond nicely to this idea of using a diabetes medication topically. Because of the network of capillaries in the skin's dermis. Topokine Therapeutics addressed this as the “sink condition”.

View attachment 388582

It’s a pharmacological term describing how specific tissues act as “sinks”, transporting the medication into the bloodstream instead of the target site. This is a prevalent effect in subcutaneous drug delivery, let alone pharmacokinetics in general.

Drug molecules will naturally move from high concentration to low concentration, so the capillaries in the dermis offer a lower concentration for the molecules to gravitate towards, which eventually lead to them entering your bloodstream. Thiazolidinediones are lipophilic, so they are literally in favor of penetrating deeply and reaching the bloodstream. They aimed to make something that could penetrate the skin enough to enter the subq layer, but WITHOUT diffusion into the capillaries.

View attachment 388583

What’s so damn splendid about their creation is how it somehow counters the sink effect. Somehow implanting the medication into the subq layer with negligible amounts of systemic exposure. The patents proved this by running multiple drug tests including Cmax, AUC, LC-MS/MS. They collected blood samples from all of the pigs they tested on. They concluded that peak plasma concentrations were about 3400 and 1300 FOLD LOWER than for oral therapy. Over the 42 day dosing period only that smidgen made it into the bloodstream.

It’s unclear how the ingredients work together to deliver the drug into the fat layer with minimal systemic exposure. But I think I figured out the mental gymnastics. If you zoom into the molecular picture, rosiglitazone is ~357 Da. According to the Dalton rule this can easily penetrate the skin barrier, and you would think with a weight like this it could easily get swelled up by the capillaries. But the ingredients all work together to swarm down the skin barrier so fast the capillary network doesn’t even see them coming. The ethanol evaporates onto your skin whilst altering the stratum corneum. After this layer is left behind, the concentrations of the other ingredients skyrocket since over 65% of the product has dissipated. The remaining propylene glycol can barely hold the drug so the liquid becomes supersaturated. The drug gets blasted through the loose dermis. The capillaries in the skin are not fenestrated. They’re continuous, and once the drug molecules reach these capillaries they ambush the microscopic transport pores. The idle lipophilic molecules immediately passively diffuse into the subcutaneous layer beneath the dermis, and they stay there.

After 42 days of using 0.3mL on 6 different treatment areas, a mean of a whopping 48% fat increase was noticed. Four mini pigs (the animal with the most similar skin to humans) were tested on.

View attachment 388584

I’m gonna shout this again. The mean fat thickness over placebo is a 48% INCREASE.

Now for the million dollar question, what’s the recipe for this topical formulation that they used?

View attachment 388585

Each one of these ingredients (aside from our tzd) are fundamentally safe for topical human use and are common ingredients in the skincare industry.

You can substitute the rosiglitazone with other thiazolidiones like pioglitazone and experiment around, but if you take the time to read the patents papers, pioglitazone in particular doesn’t give the most outstanding results. It still worked, but not as well as rosiglitazone. There’s other glitazones as well like ciglitazone. Lobeglitazone is the one that’s even stronger than rosiglitazone, and patients only take 0.5 mg of it. There’s just so many others under this drug class that people could experiment with.

Formulation ingredients:
Rosiglitazone
This is the TZD we’d be using, the patent is never actually clear on what form of rosiglitazone they used. But according to the context clues I’d say that the experiment did NOT use the malleate version (rosiglitazone malleate is the kind they use in the oral tablets), and they probably just used regular free base rosiglitazone. If they had used any specific version they would have specified. Looks like you can find rosiglitazone on this marketplace, but make SURE what you get is in free base form. https://www.echemi.com/searchGoods/temppid160705010001-rosiglitazone.html
https://www.glentham.com/en/products/product/GP6434/?utm_
https://www.chemimpex.com/products/...-8Kb6Rnp20YfaLU3IthxlarNo-QtVinjNxU4rMzQ9sfzi

Alpha-tocopherol (aka vitamin E)
is an antioxidant so that the gel doesn’t go bad. It’s unclear whether they used synthetic or natural in their experiments..but they do list exemplary antioxidants that are synthetic so I don’t think it matters. I found this gem for cheap, and it’s pure free tocopherol. You only need a very miniscule amount of this for it to do its job. Pure dl-alpha-tocopherol has a density of roughly 0.95 grams per milliliter, so you’d only need .0021ml of this stuff in the 100g formulation. Now because of the fact that that’s practically fucking impossible to measure, you’re gonna do the stock solution method to measure it (I’ll elaborate in the “how to” section)
https://www.makingcosmetics.com/VIT-VITE-01.html?lang=en_US

Anhydrous ethanol (ethanol with practically no water)
will help the product penetrate the stratum corneum as I said before. The kind they used was very pure, look for 200 proof non denatured ethanol. You’d use about 86.3mL of this per 100g of final product.
https://www.usalab.com/usa-lab-200-proof-ethanol-usp-99-97-1gal-5gal-55gal-270gal-excise-tax-included/?

As for the propylene glycol, you want very pure medical grade product asw. You’d add 26.06ml of this into the 100g batch.
https://www.walmart.com/ip/Propylen...-non-gmo-premium-natural-pure-32-oz/829649994

3.37ml of oleic acid in 100g batch
https://www.ebay.com/itm/2222473408...gdN5wKS3mgfbW8c4gSl0xzSvG3jSWrInknpDTQZPmDL-o

For the Klucel/HPC,
they don’t specify what grade they used. But from context clues, they most likely used Klucel® HF. (Edit: I don’t know why the fuck I said context clues, it literally says HF.) The formulation is supposed to be a gel, and if you added only 1g of something like EF/LF in a 10g batch, that would barely change the consistency at all. This should be weighed on a scale (favorably a four place balance, but that’s pretty expensive shit that I wouldn’t assume many of you have. A three place balance is aight instead)

https://www.kremer-pigmente.com/en/shop/mediums-binders-glues/63713-klucel-hf-pharm.html

Spoiler: How you’d actually cook this up

You’re going to want one syringe per ingredient. Cross contamination is a no no, getting everything precise is crucial. Get a nice big pack of syringes. https://www.ebay.com/itm/387000288770

https://www.premiumvials.com/30-pac...Qp_gX7QNZmwUChkbjH3VwgjSt4VcmSh_YAsvW342vvcDy

For this mixture, an amber glass mason jar works well. Since amber glass absorbs all kinds of light wavelengths. Keep that lid next to you at all times. Your mixture needs minimal exposure to air.
https://www.premiumvials.com/2-oz-a...127&gbraid=0AAAAADpaBkCcgWGovPzMQy67RBWzvL57P

Wear a mask when handling the rosiglitazone powder. You don’t want to inhale it.

The anhydrous ethanol is an ingredient you shouldn’t fuck around with, it should have MINIMAL exposure to air. The air will ruin it. The ethanol is so pure so if left exposed for the air for too long it can absorb water from the air, which fucks up your ratios and the entire point of it being “anhydrous”. Never ever leave the cap off of your ethanol bottle, it will spoil the whole thing.

And it just so happens to be the first product topokine therepeutics adds to the batch. So you should draw up all your other liquid ingredients beforehand so this entire mixing process goes as fast as possible.

You need only 2.1 µL of vitamin E. In order to measure this, you’re gonna make a 1:100 stock solution including propylene glycol. Add 9.9ml of propylene glycol and 0.1ml of vitamin e in a small vial. Now every 1 ml of the liquid has 0.01ml of vitamin E. You’d deduct 0.21ml of this stock solution with a syringe to get .0021ml of vitamin E.

Now because most of that stock solution is propylene glycol, you’re just gonna subtract that amount from your main batch to be precise and avoid any mishaps in your ratios. So you’d go 26.06ml - 0.21ml for your main propylene glycol measurement.

The first ingredient to add to the solvent beaker is 86.3ml of Anhydrous ethanol. Then after that, you’d immediately add your 25.85ml of propylene glycol, 3.37ml of oleic acid, and 0.21ml of stock solution (the vitamin E). Immediately cover your batch with the lid after adding all these. Also IMMEDIATELY put the caps back on the bottles of your chemicals, ESPECIALLY the ethanol.

Now it’s time for you to weigh out the powders. You can take your time for this part since your mixture is covered.

What sucks is you’d ideally want to use a 4 place balance to measure these out, but not a single one of those is under 100 bucks. So a cheaper 3 place scale is usually where you end up. When weighing these out, the scale should be far away from any vents, windows, fans, or anything that could possibly mess with it. Zero the scale out and you can put some weighing paper on it for the powder. Then scoop some tiny amounts of the rosiglitazone powder onto the scale. When the scale finally reads 1g, carefully funnel the weighing paper and add the powder to the batch. Stir until the liquid is clear, and then cover it back up again.

Now for the Klucel, you’re gonna weigh out 1g of it the same way you did rosiglitazone. Go over to the scale and weigh 1g. It has a relatively low bulk density, so don’t be surprised if 1g looks bulkier than it should. Dispersing this powder is incredibly important, as this is the ingredient that gives your gel its viscosity. You’re gonna uncover your batch and start whisking that shit away with a stirring rod like there’s no tomorrow. While you stir your mixture in this volatile manner, sprinkle in the Klucel. You want to scatter each dry particle of the powder throughout your mixture. Once the Klucel is all the way sprinkled in, SLOW your stirring speed to avoid bubbles. This entire dispursement should be 1-2 minutes, after that cover your shit up immediately. Remember, ethanol is a ticking time bomb.

Now, you let your batch sit. Store it in a dark cabinet away from any light (thiazolidiones are light sensitive). After 2 hours you can take it out, take the lid off and stir it for another minute. This will be the final time you stir it for the day. Then put it back and let it sit overnight.

The next day, you can begin to use your gel. It shouldn’t look cloudy/grainy, but instead uniform and smooth.

It should be stored long term in a pitch black pantry/cabinet, at a stable room temp.
View attachment 388600

Potential flaw/s: I’m sure when most of us think of volufiline, we think of something to fill recessed infras. A potential flaw with that is that the skin around the eyes is the part of the body with the thinnest skin. With how well the topical gel works, its permeability is what should make you feel weary about applying it there. A viable workaround for this would be to create an alternative formulation with less penetration enhancers.

You wouldn’t want this gel to touch your actual lower eyelid either (aegyo sal), or else you’d be giving yourself steatoblepharon. Applying a pea sized amount of the gel and rubbing it in your desired areas whilst putting tape on your lower eyelid (to ensure the gel doesn’t touch it), would be the safer way to go. Not risk free though. However applying this gel to your under eyelid is not going to wind up in the retina (causing muh macular edema). The capillaries under your eyelid don’t flow backwards towards the retina, they take blood away from the eye. What supplies the retina is the central retinal artery, which is way in the back of your eyeball in the optic nerve trunk. The actual risks here concerning applying this to the infras would be a possible increased amount of the drug in your bloodstream (from the network of ocular capillaries close to the surface of the thin skin), and the product working too well in the wrong places.

Applying it to the supras on the other hand is safer (the skin is thicker there), but you’d have to be very careful about the gel migrating or touching your actual upper eyelid. You wouldn’t want to be thickening your actual eyelid, you’d be giving yourself ptosis. A work around to this would be applying the gel right on your eyebrow, and putting tape on your eyelids just in case.

This is all hypothetical I’m not a professional don’t sue me
@Mandy? @ecoli @Histy @LaWi @Arya @Whitepill @foidslayer

TLDR?

 

[methylationnx]

TLDR?

sthu

 

[humbleMTN]

sthu

I'm sorry, what does that mean? I'm unsure if it's a typo of shut/slut or a slang

 

[moonlight1]

I’m sure everyone here has heard of volufiline, or other topicals that are marketed to give a lipofilling effect. Go check out @genio thread eviscerating volucope

Guide Volufiline: Why it's Cope and What to Do Instead

Jul 2, 2026

Volufiline: Why it's Cope and What to...​

• genio
• Replies: 40
• Forum: Looksmaxxing

• 
• 
• 

His thread mentions Rosiglitazone under non surgical procedures, which is something that’s garnered a bit of attention from this community. Rosiglitazoney is a potent PPAR-γ agonist belonging to the drug class of thiazolidiones, and it is a hidden gem for localized fat growth. I mean that literally. It was a potential product that was buried.


Mechanism

View attachment 388571

I’m sure most of us are familiar with what type 2 diabetes is. When your bodies insulin receptors become desensitized, making it harder to store energy appropriately. Because of this, people with type 2 often have higher levels of insulin since their body is trying to fight their resistance. But this obviously doesn’t last them forever, and stresses the beta cells in their pancreas to death. Well oral TZDs (Thiazolidinediones), like rosiglitazone and pioglitazone aim to work around this issue by targeting the PPAR-γ receptor (peroxisome proliferator-activated receptor gamma) which sits in the nucleus inside the cells. It indirectly helps with clearing the bloodstream of glucose/storing it, adipogenesis, and insulin sensitivity. To be more specific, when the receptor is activated, it binds and creates a heterodimer with RXR to transcribe genes.
Its change in gene expression causes more GLUT4 production which is the transporter that allows glucose to enter the cell. Hence, higher insulin sensitivity and less blood sugar. It also promotes differentiation of preadipocytes into mature adipocytes. Rosiglitazone (Avandia) is administered with a starting dose of 4mg, but if patients respond inadequately follow 8-12 weeks of treatment they can bump their dosage up to 8mg.

We don’t have tons of clinical studies conducting research on applying this in topical form onto humans, since it was created as a diabetes medication. But there are still studies about its topical use here and there that suggest its healing properties:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12023181/
https://pmc.ncbi.nlm.nih.gov/articles/PMC3733781/
https://www.cell.com/molecular-therapy-family/advances/fulltext/S3117-387X(26)00067-4
https://www.sciencedirect.com/science/article/pii/S0022202X15371050

Rosiglitazone and pioglitazone are the two main thiazolidiones that have been investigated as topicals. But there are still plenty of others under that drug class that have been researched but less extensively (ex: ciglitazone, troglitazone).

Risks
Let’s talk about practically EVERY SINGLE risk related to TZDs. Let’s keep in mind that most of these risks are minimized in the form of topical use.

1. Edema. If you’re unaware of what this is, it’s the medical term for swelling from excess fluids being trapped in your bodies tissues. The PPAR-γ receptor is not only present in regular adipocytes but it is also in kidney cells, particularly in the collecting ducts and distal tubules. The goal of the DSCT is to reabsorb more sodium chloride and water. The hormones aldosterone and ADH can act upon this. ADH will talk to dct increase water reabsorption , aldosterone will increase salt reabsorption. So remaining sodium winds up in the collecting duct to be reabsorbed. I’ll remind you of the inverse relationship between sodium and potassium- sodium pulls fluid outside of cells while potassium stores it inside. Activation of the PPAR-γ receptor causes more sodium reabsorption back into the bloodstream, and since water moves by osmosis more water is also reabsorbed. This causes a big bloated mess, and the fluid leaks into surrounding tissues. It’s specifically called peripheral edema, but there’s also other kinds of edema that have been reported. Macular edema is swelling in the macula, causing vision changes. Some of you might be aware of the fact that this has been reported before as a rare adverse affect from TZDs. But we have to keep in mind that people who have blood retinal barrier dysfunction (from their diabetes) are the ones who are at higher risk of this. Having diabetes alone usually causes a certain degree of damage to that barrier, so in most reports it’s very possible that the TZD just exacerbated a pre existing issue, and I think most of us on here are NOT diabetic. Most of the reports of macular edema even wind up being reversible, so their vision goes back to normal after stopping. This is because edema is only fluid buildup, it’s not necessarily causing permanent damage to the surrounding cells, it’s just disarranging them out of place. Now how do we work around this..? Well we’re gonna be making a TOPICAL formulation. Meaning it’s only going to work locally. If you look at all of these cases of edema, it’s from diabetics who frequently take oral TZDs as well as usually taking insulin alongside it.
2. Heart problems. If you read what I said for edema, it’s practically the same cause. The body starts to gain more fluid retention since more sodium and water get reabsorbed back into the bloodstream. More fluid starts to circulate through your bloodstream, so because of that your heart will have a heavier preload. It will have to pump a larger volume of blood. That’s why TZDs can worsen a heart that’s already weakened, or even cause new problems since overload that’s very prolonged (months to years) will stress your heart. Now how would we work around this? Well we wouldn’t even have to. A topical formation isn’t gonna give you heart failure as it only works locally
3. Increased cholesterol. Both rosiglitazone and pioglitazone lower triglycerides and increase HDL levels..but apparently rosiglitazone can increase LDL, and so can pioglitazone but to lower extents. If your body builds up too much of the bad cholesterol, it builds up in the walls of your arteries. Causing dangerous plaque to form, which narrows the artery. It can build up in very important arteries that supply blood flow to the heart and even the brain.
4. Hypertension. This is just more of the same stuff. Hypertension is the word for chronically high blood pressure, which can damage your heart and kidneys. Because of the fact that oral TZDs can cause more water and sodium reabsorption into the circulation, your blood volume will increase.
5. Hypoglycemia. This actually rarely happens when only on TZDs, but hypoglycemia is when your blood glucose levels are too low. After activating the PPAR-γ receptor, your cells will become more responsive towards insulin. Sometimes this piece alone is enough to knock someone’s blood sugar levels too low.
6. Bladder cancer. This appears as an adverse effect more specifically from pioglitazone. It’s a proposal that stemmed from studies on male rats, but human studies show little to no correlation. This possible correlation, however, is thought to be from long term exposure. From your bladder cells being repeatedly exposed to the pioglitazone metabolites.
7. Bone fracture. The stem cells inside bone marrow can either become adipocytes or osteoblasts. By activation of the PPAR-γ receptor you probably understand which kind of cell is chosen. Overtime if your body starts disproportionally making more marrow adipocytes at the expense of osteoblasts, your bones will weaken. Older women in particular are at the highest risk of this adverse effect.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5651605/

Now if you look at all of these adverse affects, you can clearly see that practically ALL of these are from oral intake. I don’t think applying a topical formulation of one of these TZDs is gonna travel all the way to your kidneys…fuck up your sodium excretion…travel to your retina…blind you permanently..so on and so forth.

The idea of topical TZDs is so convenient, that’s it’s literally been experimented with in the past. Meet Topokine Therepeutics. This biotech company experimented with creating topical rosiglitazone and other tzds in the past, as a product for local fat optimization.

https://patentimages.storage.googleapis.com/54/17/e8/fe6c9c5256bbc3/US8883834.pdf?utm

This document outlines their project. On page 33 you can see the results of the experiments they conducted. They experimented with creating formulations with different kinds of thiazolidinediones, including formulations containing 0.1% and 0.3% rosiglitazone. Incredible results were revealed.

In order to create a topical formulation for this, it’s important that it reaches the subcutaneous layer without being systemically absorbed through your bloodstream. That’s probably the main reason why the project was abandoned, the critics of it didn’t think the public would respond nicely to this idea of using a diabetes medication topically. Because of the network of capillaries in the skin's dermis. Topokine Therapeutics addressed this as the “sink condition”.

View attachment 388582

It’s a pharmacological term describing how specific tissues act as “sinks”, transporting the medication into the bloodstream instead of the target site. This is a prevalent effect in subcutaneous drug delivery, let alone pharmacokinetics in general.

Drug molecules will naturally move from high concentration to low concentration, so the capillaries in the dermis offer a lower concentration for the molecules to gravitate towards, which eventually lead to them entering your bloodstream. Thiazolidinediones are lipophilic, so they are literally in favor of penetrating deeply and reaching the bloodstream. They aimed to make something that could penetrate the skin enough to enter the subq layer, but WITHOUT diffusion into the capillaries.

View attachment 388583

What’s so damn splendid about their creation is how it somehow counters the sink effect. Somehow implanting the medication into the subq layer with negligible amounts of systemic exposure. The patents proved this by running multiple drug tests including Cmax, AUC, LC-MS/MS. They collected blood samples from all of the pigs they tested on. They concluded that peak plasma concentrations were about 3400 and 1300 FOLD LOWER than for oral therapy. Over the 42 day dosing period only that smidgen made it into the bloodstream.

It’s unclear how the ingredients work together to deliver the drug into the fat layer with minimal systemic exposure. But I think I figured out the mental gymnastics. If you zoom into the molecular picture, rosiglitazone is ~357 Da. According to the Dalton rule this can easily penetrate the skin barrier, and you would think with a weight like this it could easily get swelled up by the capillaries. But the ingredients all work together to swarm down the skin barrier so fast the capillary network doesn’t even see them coming. The ethanol evaporates onto your skin whilst altering the stratum corneum. After this layer is left behind, the concentrations of the other ingredients skyrocket since over 65% of the product has dissipated. The remaining propylene glycol can barely hold the drug so the liquid becomes supersaturated. The drug gets blasted through the loose dermis. The capillaries in the skin are not fenestrated. They’re continuous, and once the drug molecules reach these capillaries they ambush the microscopic transport pores. The idle lipophilic molecules immediately passively diffuse into the subcutaneous layer beneath the dermis, and they stay there.

After 42 days of using 0.3mL on 6 different treatment areas, a mean of a whopping 48% fat increase was noticed. Four mini pigs (the animal with the most similar skin to humans) were tested on.

View attachment 388584

I’m gonna shout this again. The mean fat thickness over placebo is a 48% INCREASE.

Now for the million dollar question, what’s the recipe for this topical formulation that they used?

View attachment 388585

Each one of these ingredients (aside from our tzd) are fundamentally safe for topical human use and are common ingredients in the skincare industry.

You can substitute the rosiglitazone with other thiazolidiones like pioglitazone and experiment around, but if you take the time to read the patents papers, pioglitazone in particular doesn’t give the most outstanding results. It still worked, but not as well as rosiglitazone. There’s other glitazones as well like ciglitazone. Lobeglitazone is the one that’s even stronger than rosiglitazone, and patients only take 0.5 mg of it. There’s just so many others under this drug class that people could experiment with.

Formulation ingredients:
Rosiglitazone
This is the TZD we’d be using, the patent is never actually clear on what form of rosiglitazone they used. But according to the context clues I’d say that the experiment did NOT use the malleate version (rosiglitazone malleate is the kind they use in the oral tablets), and they probably just used regular free base rosiglitazone. If they had used any specific version they would have specified. Looks like you can find rosiglitazone on this marketplace, but make SURE what you get is in free base form. https://www.echemi.com/searchGoods/temppid160705010001-rosiglitazone.html
https://www.glentham.com/en/products/product/GP6434/?utm_
https://www.chemimpex.com/products/...-8Kb6Rnp20YfaLU3IthxlarNo-QtVinjNxU4rMzQ9sfzi

Alpha-tocopherol (aka vitamin E)
is an antioxidant so that the gel doesn’t go bad. It’s unclear whether they used synthetic or natural in their experiments..but they do list exemplary antioxidants that are synthetic so I don’t think it matters. I found this gem for cheap, and it’s pure free tocopherol. You only need a very miniscule amount of this for it to do its job. Pure dl-alpha-tocopherol has a density of roughly 0.95 grams per milliliter, so you’d only need .0021ml of this stuff in the 100g formulation. Now because of the fact that that’s practically fucking impossible to measure, you’re gonna do the stock solution method to measure it (I’ll elaborate in the “how to” section)
https://www.makingcosmetics.com/VIT-VITE-01.html?lang=en_US

Anhydrous ethanol (ethanol with practically no water)
will help the product penetrate the stratum corneum as I said before. The kind they used was very pure, look for 200 proof non denatured ethanol. You’d use about 86.3mL of this per 100g of final product.
https://www.usalab.com/usa-lab-200-proof-ethanol-usp-99-97-1gal-5gal-55gal-270gal-excise-tax-included/?

As for the propylene glycol, you want very pure medical grade product asw. You’d add 26.06ml of this into the 100g batch.
https://www.walmart.com/ip/Propylen...-non-gmo-premium-natural-pure-32-oz/829649994

3.37ml of oleic acid in 100g batch
https://www.ebay.com/itm/2222473408...gdN5wKS3mgfbW8c4gSl0xzSvG3jSWrInknpDTQZPmDL-o

For the Klucel/HPC,
they don’t specify what grade they used. But from context clues, they most likely used Klucel® HF. (Edit: I don’t know why the fuck I said context clues, it literally says HF.) The formulation is supposed to be a gel, and if you added only 1g of something like EF/LF in a 10g batch, that would barely change the consistency at all. This should be weighed on a scale (favorably a four place balance, but that’s pretty expensive shit that I wouldn’t assume many of you have. A three place balance is aight instead)

https://www.kremer-pigmente.com/en/shop/mediums-binders-glues/63713-klucel-hf-pharm.html

Spoiler: How you’d actually cook this up

You’re going to want one syringe per ingredient. Cross contamination is a no no, getting everything precise is crucial. Get a nice big pack of syringes. https://www.ebay.com/itm/387000288770

https://www.premiumvials.com/30-pac...Qp_gX7QNZmwUChkbjH3VwgjSt4VcmSh_YAsvW342vvcDy

For this mixture, an amber glass mason jar works well. Since amber glass absorbs all kinds of light wavelengths. Keep that lid next to you at all times. Your mixture needs minimal exposure to air.
https://www.premiumvials.com/2-oz-a...127&gbraid=0AAAAADpaBkCcgWGovPzMQy67RBWzvL57P

Wear a mask when handling the rosiglitazone powder. You don’t want to inhale it.

The anhydrous ethanol is an ingredient you shouldn’t fuck around with, it should have MINIMAL exposure to air. The air will ruin it. The ethanol is so pure so if left exposed for the air for too long it can absorb water from the air, which fucks up your ratios and the entire point of it being “anhydrous”. Never ever leave the cap off of your ethanol bottle, it will spoil the whole thing.

And it just so happens to be the first product topokine therepeutics adds to the batch. So you should draw up all your other liquid ingredients beforehand so this entire mixing process goes as fast as possible.

You need only 2.1 µL of vitamin E. In order to measure this, you’re gonna make a 1:100 stock solution including propylene glycol. Add 9.9ml of propylene glycol and 0.1ml of vitamin e in a small vial. Now every 1 ml of the liquid has 0.01ml of vitamin E. You’d deduct 0.21ml of this stock solution with a syringe to get .0021ml of vitamin E.

Now because most of that stock solution is propylene glycol, you’re just gonna subtract that amount from your main batch to be precise and avoid any mishaps in your ratios. So you’d go 26.06ml - 0.21ml for your main propylene glycol measurement.

The first ingredient to add to the solvent beaker is 86.3ml of Anhydrous ethanol. Then after that, you’d immediately add your 25.85ml of propylene glycol, 3.37ml of oleic acid, and 0.21ml of stock solution (the vitamin E). Immediately cover your batch with the lid after adding all these. Also IMMEDIATELY put the caps back on the bottles of your chemicals, ESPECIALLY the ethanol.

Now it’s time for you to weigh out the powders. You can take your time for this part since your mixture is covered.

What sucks is you’d ideally want to use a 4 place balance to measure these out, but not a single one of those is under 100 bucks. So a cheaper 3 place scale is usually where you end up. When weighing these out, the scale should be far away from any vents, windows, fans, or anything that could possibly mess with it. Zero the scale out and you can put some weighing paper on it for the powder. Then scoop some tiny amounts of the rosiglitazone powder onto the scale. When the scale finally reads 1g, carefully funnel the weighing paper and add the powder to the batch. Stir until the liquid is clear, and then cover it back up again.

Now for the Klucel, you’re gonna weigh out 1g of it the same way you did rosiglitazone. Go over to the scale and weigh 1g. It has a relatively low bulk density, so don’t be surprised if 1g looks bulkier than it should. Dispersing this powder is incredibly important, as this is the ingredient that gives your gel its viscosity. You’re gonna uncover your batch and start whisking that shit away with a stirring rod like there’s no tomorrow. While you stir your mixture in this volatile manner, sprinkle in the Klucel. You want to scatter each dry particle of the powder throughout your mixture. Once the Klucel is all the way sprinkled in, SLOW your stirring speed to avoid bubbles. This entire dispursement should be 1-2 minutes, after that cover your shit up immediately. Remember, ethanol is a ticking time bomb.

Now, you let your batch sit. Store it in a dark cabinet away from any light (thiazolidiones are light sensitive). After 2 hours you can take it out, take the lid off and stir it for another minute. This will be the final time you stir it for the day. Then put it back and let it sit overnight.

The next day, you can begin to use your gel. It shouldn’t look cloudy/grainy, but instead uniform and smooth.

It should be stored long term in a pitch black pantry/cabinet, at a stable room temp.
View attachment 388600

Potential flaw/s: I’m sure when most of us think of volufiline, we think of something to fill recessed infras. A potential flaw with that is that the skin around the eyes is the part of the body with the thinnest skin. With how well the topical gel works, its permeability is what should make you feel weary about applying it there. A viable workaround for this would be to create an alternative formulation with less penetration enhancers.

You wouldn’t want this gel to touch your actual lower eyelid either (aegyo sal), or else you’d be giving yourself steatoblepharon. Applying a pea sized amount of the gel and rubbing it in your desired areas whilst putting tape on your lower eyelid (to ensure the gel doesn’t touch it), would be the safer way to go. Not risk free though. However applying this gel to your under eyelid is not going to wind up in the retina (causing muh macular edema). The capillaries under your eyelid don’t flow backwards towards the retina, they take blood away from the eye. What supplies the retina is the central retinal artery, which is way in the back of your eyeball in the optic nerve trunk. The actual risks here concerning applying this to the infras would be a possible increased amount of the drug in your bloodstream (from the network of ocular capillaries close to the surface of the thin skin), and the product working too well in the wrong places.

Applying it to the supras on the other hand is safer (the skin is thicker there), but you’d have to be very careful about the gel migrating or touching your actual upper eyelid. You wouldn’t want to be thickening your actual eyelid, you’d be giving yourself ptosis. A work around to this would be applying the gel right on your eyebrow, and putting tape on your eyelids just in case.

This is all hypothetical I’m not a professional don’t sue me
@Mandy? @ecoli @Histy @LaWi @Arya @Whitepill @foidslayer

can i apply it on my boobs

 

[giga.mia]

can i apply it on my boobs

Ideally

 

[jacksasub5]

I’m sure everyone here has heard of volufiline, or other topicals that are marketed to give a lipofilling effect. Go check out @genio thread eviscerating volucope

Guide Volufiline: Why it's Cope and What to Do Instead

Jul 2, 2026

Volufiline: Why it's Cope and What to...​

• genio
• Replies: 40
• Forum: Looksmaxxing

• 
• 
• 

His thread mentions Rosiglitazone under non surgical procedures, which is something that’s garnered a bit of attention from this community. Rosiglitazoney is a potent PPAR-γ agonist belonging to the drug class of thiazolidiones, and it is a hidden gem for localized fat growth. I mean that literally. It was a potential product that was buried.


Mechanism

View attachment 388571

I’m sure most of us are familiar with what type 2 diabetes is. When your bodies insulin receptors become desensitized, making it harder to store energy appropriately. Because of this, people with type 2 often have higher levels of insulin since their body is trying to fight their resistance. But this obviously doesn’t last them forever, and stresses the beta cells in their pancreas to death. Well oral TZDs (Thiazolidinediones), like rosiglitazone and pioglitazone aim to work around this issue by targeting the PPAR-γ receptor (peroxisome proliferator-activated receptor gamma) which sits in the nucleus inside the cells. It indirectly helps with clearing the bloodstream of glucose/storing it, adipogenesis, and insulin sensitivity. To be more specific, when the receptor is activated, it binds and creates a heterodimer with RXR to transcribe genes.
Its change in gene expression causes more GLUT4 production which is the transporter that allows glucose to enter the cell. Hence, higher insulin sensitivity and less blood sugar. It also promotes differentiation of preadipocytes into mature adipocytes. Rosiglitazone (Avandia) is administered with a starting dose of 4mg, but if patients respond inadequately follow 8-12 weeks of treatment they can bump their dosage up to 8mg.

We don’t have tons of clinical studies conducting research on applying this in topical form onto humans, since it was created as a diabetes medication. But there are still studies about its topical use here and there that suggest its healing properties:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12023181/
https://pmc.ncbi.nlm.nih.gov/articles/PMC3733781/
https://www.cell.com/molecular-therapy-family/advances/fulltext/S3117-387X(26)00067-4
https://www.sciencedirect.com/science/article/pii/S0022202X15371050

Rosiglitazone and pioglitazone are the two main thiazolidiones that have been investigated as topicals. But there are still plenty of others under that drug class that have been researched but less extensively (ex: ciglitazone, troglitazone).

Risks
Let’s talk about practically EVERY SINGLE risk related to TZDs. Let’s keep in mind that most of these risks are minimized in the form of topical use.

1. Edema. If you’re unaware of what this is, it’s the medical term for swelling from excess fluids being trapped in your bodies tissues. The PPAR-γ receptor is not only present in regular adipocytes but it is also in kidney cells, particularly in the collecting ducts and distal tubules. The goal of the DSCT is to reabsorb more sodium chloride and water. The hormones aldosterone and ADH can act upon this. ADH will talk to dct increase water reabsorption , aldosterone will increase salt reabsorption. So remaining sodium winds up in the collecting duct to be reabsorbed. I’ll remind you of the inverse relationship between sodium and potassium- sodium pulls fluid outside of cells while potassium stores it inside. Activation of the PPAR-γ receptor causes more sodium reabsorption back into the bloodstream, and since water moves by osmosis more water is also reabsorbed. This causes a big bloated mess, and the fluid leaks into surrounding tissues. It’s specifically called peripheral edema, but there’s also other kinds of edema that have been reported. Macular edema is swelling in the macula, causing vision changes. Some of you might be aware of the fact that this has been reported before as a rare adverse affect from TZDs. But we have to keep in mind that people who have blood retinal barrier dysfunction (from their diabetes) are the ones who are at higher risk of this. Having diabetes alone usually causes a certain degree of damage to that barrier, so in most reports it’s very possible that the TZD just exacerbated a pre existing issue, and I think most of us on here are NOT diabetic. Most of the reports of macular edema even wind up being reversible, so their vision goes back to normal after stopping. This is because edema is only fluid buildup, it’s not necessarily causing permanent damage to the surrounding cells, it’s just disarranging them out of place. Now how do we work around this..? Well we’re gonna be making a TOPICAL formulation. Meaning it’s only going to work locally. If you look at all of these cases of edema, it’s from diabetics who frequently take oral TZDs as well as usually taking insulin alongside it.
2. Heart problems. If you read what I said for edema, it’s practically the same cause. The body starts to gain more fluid retention since more sodium and water get reabsorbed back into the bloodstream. More fluid starts to circulate through your bloodstream, so because of that your heart will have a heavier preload. It will have to pump a larger volume of blood. That’s why TZDs can worsen a heart that’s already weakened, or even cause new problems since overload that’s very prolonged (months to years) will stress your heart. Now how would we work around this? Well we wouldn’t even have to. A topical formation isn’t gonna give you heart failure as it only works locally
3. Increased cholesterol. Both rosiglitazone and pioglitazone lower triglycerides and increase HDL levels..but apparently rosiglitazone can increase LDL, and so can pioglitazone but to lower extents. If your body builds up too much of the bad cholesterol, it builds up in the walls of your arteries. Causing dangerous plaque to form, which narrows the artery. It can build up in very important arteries that supply blood flow to the heart and even the brain.
4. Hypertension. This is just more of the same stuff. Hypertension is the word for chronically high blood pressure, which can damage your heart and kidneys. Because of the fact that oral TZDs can cause more water and sodium reabsorption into the circulation, your blood volume will increase.
5. Hypoglycemia. This actually rarely happens when only on TZDs, but hypoglycemia is when your blood glucose levels are too low. After activating the PPAR-γ receptor, your cells will become more responsive towards insulin. Sometimes this piece alone is enough to knock someone’s blood sugar levels too low.
6. Bladder cancer. This appears as an adverse effect more specifically from pioglitazone. It’s a proposal that stemmed from studies on male rats, but human studies show little to no correlation. This possible correlation, however, is thought to be from long term exposure. From your bladder cells being repeatedly exposed to the pioglitazone metabolites.
7. Bone fracture. The stem cells inside bone marrow can either become adipocytes or osteoblasts. By activation of the PPAR-γ receptor you probably understand which kind of cell is chosen. Overtime if your body starts disproportionally making more marrow adipocytes at the expense of osteoblasts, your bones will weaken. Older women in particular are at the highest risk of this adverse effect.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5651605/

Now if you look at all of these adverse affects, you can clearly see that practically ALL of these are from oral intake. I don’t think applying a topical formulation of one of these TZDs is gonna travel all the way to your kidneys…fuck up your sodium excretion…travel to your retina…blind you permanently..so on and so forth.

The idea of topical TZDs is so convenient, that’s it’s literally been experimented with in the past. Meet Topokine Therepeutics. This biotech company experimented with creating topical rosiglitazone and other tzds in the past, as a product for local fat optimization.

https://patentimages.storage.googleapis.com/54/17/e8/fe6c9c5256bbc3/US8883834.pdf?utm

This document outlines their project. On page 33 you can see the results of the experiments they conducted. They experimented with creating formulations with different kinds of thiazolidinediones, including formulations containing 0.1% and 0.3% rosiglitazone. Incredible results were revealed.

In order to create a topical formulation for this, it’s important that it reaches the subcutaneous layer without being systemically absorbed through your bloodstream. That’s probably the main reason why the project was abandoned, the critics of it didn’t think the public would respond nicely to this idea of using a diabetes medication topically. Because of the network of capillaries in the skin's dermis. Topokine Therapeutics addressed this as the “sink condition”.

View attachment 388582

It’s a pharmacological term describing how specific tissues act as “sinks”, transporting the medication into the bloodstream instead of the target site. This is a prevalent effect in subcutaneous drug delivery, let alone pharmacokinetics in general.

Drug molecules will naturally move from high concentration to low concentration, so the capillaries in the dermis offer a lower concentration for the molecules to gravitate towards, which eventually lead to them entering your bloodstream. Thiazolidinediones are lipophilic, so they are literally in favor of penetrating deeply and reaching the bloodstream. They aimed to make something that could penetrate the skin enough to enter the subq layer, but WITHOUT diffusion into the capillaries.

View attachment 388583

What’s so damn splendid about their creation is how it somehow counters the sink effect. Somehow implanting the medication into the subq layer with negligible amounts of systemic exposure. The patents proved this by running multiple drug tests including Cmax, AUC, LC-MS/MS. They collected blood samples from all of the pigs they tested on. They concluded that peak plasma concentrations were about 3400 and 1300 FOLD LOWER than for oral therapy. Over the 42 day dosing period only that smidgen made it into the bloodstream.

It’s unclear how the ingredients work together to deliver the drug into the fat layer with minimal systemic exposure. But I think I figured out the mental gymnastics. If you zoom into the molecular picture, rosiglitazone is ~357 Da. According to the Dalton rule this can easily penetrate the skin barrier, and you would think with a weight like this it could easily get swelled up by the capillaries. But the ingredients all work together to swarm down the skin barrier so fast the capillary network doesn’t even see them coming. The ethanol evaporates onto your skin whilst altering the stratum corneum. After this layer is left behind, the concentrations of the other ingredients skyrocket since over 65% of the product has dissipated. The remaining propylene glycol can barely hold the drug so the liquid becomes supersaturated. The drug gets blasted through the loose dermis. The capillaries in the skin are not fenestrated. They’re continuous, and once the drug molecules reach these capillaries they ambush the microscopic transport pores. The idle lipophilic molecules immediately passively diffuse into the subcutaneous layer beneath the dermis, and they stay there.

After 42 days of using 0.3mL on 6 different treatment areas, a mean of a whopping 48% fat increase was noticed. Four mini pigs (the animal with the most similar skin to humans) were tested on.

View attachment 388584

I’m gonna shout this again. The mean fat thickness over placebo is a 48% INCREASE.

Now for the million dollar question, what’s the recipe for this topical formulation that they used?

View attachment 388585

Each one of these ingredients (aside from our tzd) are fundamentally safe for topical human use and are common ingredients in the skincare industry.

You can substitute the rosiglitazone with other thiazolidiones like pioglitazone and experiment around, but if you take the time to read the patents papers, pioglitazone in particular doesn’t give the most outstanding results. It still worked, but not as well as rosiglitazone. There’s other glitazones as well like ciglitazone. Lobeglitazone is the one that’s even stronger than rosiglitazone, and patients only take 0.5 mg of it. There’s just so many others under this drug class that people could experiment with.

Formulation ingredients:
Rosiglitazone
This is the TZD we’d be using, the patent is never actually clear on what form of rosiglitazone they used. But according to the context clues I’d say that the experiment did NOT use the malleate version (rosiglitazone malleate is the kind they use in the oral tablets), and they probably just used regular free base rosiglitazone. If they had used any specific version they would have specified. Looks like you can find rosiglitazone on this marketplace, but make SURE what you get is in free base form. https://www.echemi.com/searchGoods/temppid160705010001-rosiglitazone.html
https://www.glentham.com/en/products/product/GP6434/?utm_
https://www.chemimpex.com/products/...-8Kb6Rnp20YfaLU3IthxlarNo-QtVinjNxU4rMzQ9sfzi

Alpha-tocopherol (aka vitamin E)
is an antioxidant so that the gel doesn’t go bad. It’s unclear whether they used synthetic or natural in their experiments..but they do list exemplary antioxidants that are synthetic so I don’t think it matters. I found this gem for cheap, and it’s pure free tocopherol. You only need a very miniscule amount of this for it to do its job. Pure dl-alpha-tocopherol has a density of roughly 0.95 grams per milliliter, so you’d only need .0021ml of this stuff in the 100g formulation. Now because of the fact that that’s practically fucking impossible to measure, you’re gonna do the stock solution method to measure it (I’ll elaborate in the “how to” section)
https://www.makingcosmetics.com/VIT-VITE-01.html?lang=en_US

Anhydrous ethanol (ethanol with practically no water)
will help the product penetrate the stratum corneum as I said before. The kind they used was very pure, look for 200 proof non denatured ethanol. You’d use about 86.3mL of this per 100g of final product.
https://www.usalab.com/usa-lab-200-proof-ethanol-usp-99-97-1gal-5gal-55gal-270gal-excise-tax-included/?

As for the propylene glycol, you want very pure medical grade product asw. You’d add 26.06ml of this into the 100g batch.
https://www.walmart.com/ip/Propylen...-non-gmo-premium-natural-pure-32-oz/829649994

3.37ml of oleic acid in 100g batch
https://www.ebay.com/itm/2222473408...gdN5wKS3mgfbW8c4gSl0xzSvG3jSWrInknpDTQZPmDL-o

For the Klucel/HPC,
they don’t specify what grade they used. But from context clues, they most likely used Klucel® HF. (Edit: I don’t know why the fuck I said context clues, it literally says HF.) The formulation is supposed to be a gel, and if you added only 1g of something like EF/LF in a 10g batch, that would barely change the consistency at all. This should be weighed on a scale (favorably a four place balance, but that’s pretty expensive shit that I wouldn’t assume many of you have. A three place balance is aight instead)

https://www.kremer-pigmente.com/en/shop/mediums-binders-glues/63713-klucel-hf-pharm.html

Spoiler: How you’d actually cook this up

You’re going to want one syringe per ingredient. Cross contamination is a no no, getting everything precise is crucial. Get a nice big pack of syringes. https://www.ebay.com/itm/387000288770

https://www.premiumvials.com/30-pac...Qp_gX7QNZmwUChkbjH3VwgjSt4VcmSh_YAsvW342vvcDy

For this mixture, an amber glass mason jar works well. Since amber glass absorbs all kinds of light wavelengths. Keep that lid next to you at all times. Your mixture needs minimal exposure to air.
https://www.premiumvials.com/2-oz-a...127&gbraid=0AAAAADpaBkCcgWGovPzMQy67RBWzvL57P

Wear a mask when handling the rosiglitazone powder. You don’t want to inhale it.

The anhydrous ethanol is an ingredient you shouldn’t fuck around with, it should have MINIMAL exposure to air. The air will ruin it. The ethanol is so pure so if left exposed for the air for too long it can absorb water from the air, which fucks up your ratios and the entire point of it being “anhydrous”. Never ever leave the cap off of your ethanol bottle, it will spoil the whole thing.

And it just so happens to be the first product topokine therepeutics adds to the batch. So you should draw up all your other liquid ingredients beforehand so this entire mixing process goes as fast as possible.

You need only 2.1 µL of vitamin E. In order to measure this, you’re gonna make a 1:100 stock solution including propylene glycol. Add 9.9ml of propylene glycol and 0.1ml of vitamin e in a small vial. Now every 1 ml of the liquid has 0.01ml of vitamin E. You’d deduct 0.21ml of this stock solution with a syringe to get .0021ml of vitamin E.

Now because most of that stock solution is propylene glycol, you’re just gonna subtract that amount from your main batch to be precise and avoid any mishaps in your ratios. So you’d go 26.06ml - 0.21ml for your main propylene glycol measurement.

The first ingredient to add to the solvent beaker is 86.3ml of Anhydrous ethanol. Then after that, you’d immediately add your 25.85ml of propylene glycol, 3.37ml of oleic acid, and 0.21ml of stock solution (the vitamin E). Immediately cover your batch with the lid after adding all these. Also IMMEDIATELY put the caps back on the bottles of your chemicals, ESPECIALLY the ethanol.

Now it’s time for you to weigh out the powders. You can take your time for this part since your mixture is covered.

What sucks is you’d ideally want to use a 4 place balance to measure these out, but not a single one of those is under 100 bucks. So a cheaper 3 place scale is usually where you end up. When weighing these out, the scale should be far away from any vents, windows, fans, or anything that could possibly mess with it. Zero the scale out and you can put some weighing paper on it for the powder. Then scoop some tiny amounts of the rosiglitazone powder onto the scale. When the scale finally reads 1g, carefully funnel the weighing paper and add the powder to the batch. Stir until the liquid is clear, and then cover it back up again.

Now for the Klucel, you’re gonna weigh out 1g of it the same way you did rosiglitazone. Go over to the scale and weigh 1g. It has a relatively low bulk density, so don’t be surprised if 1g looks bulkier than it should. Dispersing this powder is incredibly important, as this is the ingredient that gives your gel its viscosity. You’re gonna uncover your batch and start whisking that shit away with a stirring rod like there’s no tomorrow. While you stir your mixture in this volatile manner, sprinkle in the Klucel. You want to scatter each dry particle of the powder throughout your mixture. Once the Klucel is all the way sprinkled in, SLOW your stirring speed to avoid bubbles. This entire dispursement should be 1-2 minutes, after that cover your shit up immediately. Remember, ethanol is a ticking time bomb.

Now, you let your batch sit. Store it in a dark cabinet away from any light (thiazolidiones are light sensitive). After 2 hours you can take it out, take the lid off and stir it for another minute. This will be the final time you stir it for the day. Then put it back and let it sit overnight.

The next day, you can begin to use your gel. It shouldn’t look cloudy/grainy, but instead uniform and smooth.

It should be stored long term in a pitch black pantry/cabinet, at a stable room temp.
View attachment 388600

Potential flaw/s: I’m sure when most of us think of volufiline, we think of something to fill recessed infras. A potential flaw with that is that the skin around the eyes is the part of the body with the thinnest skin. With how well the topical gel works, its permeability is what should make you feel weary about applying it there. A viable workaround for this would be to create an alternative formulation with less penetration enhancers.

You wouldn’t want this gel to touch your actual lower eyelid either (aegyo sal), or else you’d be giving yourself steatoblepharon. Applying a pea sized amount of the gel and rubbing it in your desired areas whilst putting tape on your lower eyelid (to ensure the gel doesn’t touch it), would be the safer way to go. Not risk free though. However applying this gel to your under eyelid is not going to wind up in the retina (causing muh macular edema). The capillaries under your eyelid don’t flow backwards towards the retina, they take blood away from the eye. What supplies the retina is the central retinal artery, which is way in the back of your eyeball in the optic nerve trunk. The actual risks here concerning applying this to the infras would be a possible increased amount of the drug in your bloodstream (from the network of ocular capillaries close to the surface of the thin skin), and the product working too well in the wrong places.

Applying it to the supras on the other hand is safer (the skin is thicker there), but you’d have to be very careful about the gel migrating or touching your actual upper eyelid. You wouldn’t want to be thickening your actual eyelid, you’d be giving yourself ptosis. A work around to this would be applying the gel right on your eyebrow, and putting tape on your eyelids just in case.

This is all hypothetical I’m not a professional don’t sue me
@Mandy? @ecoli @Histy @LaWi @Arya @Whitepill @foidslayer

dnr waaaay to much words

 

[otter]

Wow this is fascinating.

I wonder if I used this during a caloric deficit? Would facial fat grow anyways or grow new but empty fat cells that would inflate in the future?

I think topekine used roglitzione because pioglitzione converts to an active metabolite in the liver that last 3 to 4 times longer than poglitzione itself meaning onger systemic effects.

One may have to be careful so topical retinoids don't penetrate skin super deeply with this and get into fat pads. Retinoids block pre adipocyte differentiation and downregulate glut4, the opposite of what we want.


Two other possible ingredients to add.

Myristl nicotinamide is an ingredient common in skin barrier repair creams. It's a fat soluble ester that slowly releases niacin. The niacin will block HSL to prevent fat loss when calories aren't high

Estradiol upregulates adrenergic a2 receptors that puts a brake on HSL triggered by catecholamines.

Roglitzione increases glut4 proteins which bring glucose into fat cells when the glut4 is triggered by insulin. Estradiol is a lesser trigger of glut4 release too.

Unfortunately if estradiol goes systemic you might do something scandalizing and regrettable like order a subscription to the Hallmark channel. That's my 9th greatest fear.

 

[otter]

And also, progesterone increases the number of Ppary receptors making your fat cells more sensitive to roglitzione..
Progesterone also decreases HSL

I think myrstil nicotinamide would be a good idea If you don't want to add hormones like e2 or P and are not in a calorie surplus.

 

[alkobarti]

It would ideally be the same as the formula for rosi I’m working on

How's the eye stuff going btw

 

[otter]

Have you tried this glitza-fine yet?

 

[victorique]

I’m sure everyone here has heard of volufiline, or other topicals that are marketed to give a lipofilling effect. Go check out @genio thread eviscerating volucope

Guide Volufiline: Why it's Cope and What to Do Instead

Jul 2, 2026

Volufiline: Why it's Cope and What to...​

• genio
• Replies: 40
• Forum: Looksmaxxing

• 
• 
• 

His thread mentions Rosiglitazone under non surgical procedures, which is something that’s garnered a bit of attention from this community. Rosiglitazoney is a potent PPAR-γ agonist belonging to the drug class of thiazolidiones, and it is a hidden gem for localized fat growth. I mean that literally. It was a potential product that was buried.


Mechanism

View attachment 388571

I’m sure most of us are familiar with what type 2 diabetes is. When your bodies insulin receptors become desensitized, making it harder to store energy appropriately. Because of this, people with type 2 often have higher levels of insulin since their body is trying to fight their resistance. But this obviously doesn’t last them forever, and stresses the beta cells in their pancreas to death. Well oral TZDs (Thiazolidinediones), like rosiglitazone and pioglitazone aim to work around this issue by targeting the PPAR-γ receptor (peroxisome proliferator-activated receptor gamma) which sits in the nucleus inside the cells. It indirectly helps with clearing the bloodstream of glucose/storing it, adipogenesis, and insulin sensitivity. To be more specific, when the receptor is activated, it binds and creates a heterodimer with RXR to transcribe genes.
Its change in gene expression causes more GLUT4 production which is the transporter that allows glucose to enter the cell. Hence, higher insulin sensitivity and less blood sugar. It also promotes differentiation of preadipocytes into mature adipocytes. Rosiglitazone (Avandia) is administered with a starting dose of 4mg, but if patients respond inadequately follow 8-12 weeks of treatment they can bump their dosage up to 8mg.

We don’t have tons of clinical studies conducting research on applying this in topical form onto humans, since it was created as a diabetes medication. But there are still studies about its topical use here and there that suggest its healing properties:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12023181/
https://pmc.ncbi.nlm.nih.gov/articles/PMC3733781/
https://www.cell.com/molecular-therapy-family/advances/fulltext/S3117-387X(26)00067-4
https://www.sciencedirect.com/science/article/pii/S0022202X15371050

Rosiglitazone and pioglitazone are the two main thiazolidiones that have been investigated as topicals. But there are still plenty of others under that drug class that have been researched but less extensively (ex: ciglitazone, troglitazone).

Risks
Let’s talk about practically EVERY SINGLE risk related to TZDs. Let’s keep in mind that most of these risks are minimized in the form of topical use.

1. Edema. If you’re unaware of what this is, it’s the medical term for swelling from excess fluids being trapped in your bodies tissues. The PPAR-γ receptor is not only present in regular adipocytes but it is also in kidney cells, particularly in the collecting ducts and distal tubules. The goal of the DSCT is to reabsorb more sodium chloride and water. The hormones aldosterone and ADH can act upon this. ADH will talk to dct increase water reabsorption , aldosterone will increase salt reabsorption. So remaining sodium winds up in the collecting duct to be reabsorbed. I’ll remind you of the inverse relationship between sodium and potassium- sodium pulls fluid outside of cells while potassium stores it inside. Activation of the PPAR-γ receptor causes more sodium reabsorption back into the bloodstream, and since water moves by osmosis more water is also reabsorbed. This causes a big bloated mess, and the fluid leaks into surrounding tissues. It’s specifically called peripheral edema, but there’s also other kinds of edema that have been reported. Macular edema is swelling in the macula, causing vision changes. Some of you might be aware of the fact that this has been reported before as a rare adverse affect from TZDs. But we have to keep in mind that people who have blood retinal barrier dysfunction (from their diabetes) are the ones who are at higher risk of this. Having diabetes alone usually causes a certain degree of damage to that barrier, so in most reports it’s very possible that the TZD just exacerbated a pre existing issue, and I think most of us on here are NOT diabetic. Most of the reports of macular edema even wind up being reversible, so their vision goes back to normal after stopping. This is because edema is only fluid buildup, it’s not necessarily causing permanent damage to the surrounding cells, it’s just disarranging them out of place. Now how do we work around this..? Well we’re gonna be making a TOPICAL formulation. Meaning it’s only going to work locally. If you look at all of these cases of edema, it’s from diabetics who frequently take oral TZDs as well as usually taking insulin alongside it.
2. Heart problems. If you read what I said for edema, it’s practically the same cause. The body starts to gain more fluid retention since more sodium and water get reabsorbed back into the bloodstream. More fluid starts to circulate through your bloodstream, so because of that your heart will have a heavier preload. It will have to pump a larger volume of blood. That’s why TZDs can worsen a heart that’s already weakened, or even cause new problems since overload that’s very prolonged (months to years) will stress your heart. Now how would we work around this? Well we wouldn’t even have to. A topical formation isn’t gonna give you heart failure as it only works locally
3. Increased cholesterol. Both rosiglitazone and pioglitazone lower triglycerides and increase HDL levels..but apparently rosiglitazone can increase LDL, and so can pioglitazone but to lower extents. If your body builds up too much of the bad cholesterol, it builds up in the walls of your arteries. Causing dangerous plaque to form, which narrows the artery. It can build up in very important arteries that supply blood flow to the heart and even the brain.
4. Hypertension. This is just more of the same stuff. Hypertension is the word for chronically high blood pressure, which can damage your heart and kidneys. Because of the fact that oral TZDs can cause more water and sodium reabsorption into the circulation, your blood volume will increase.
5. Hypoglycemia. This actually rarely happens when only on TZDs, but hypoglycemia is when your blood glucose levels are too low. After activating the PPAR-γ receptor, your cells will become more responsive towards insulin. Sometimes this piece alone is enough to knock someone’s blood sugar levels too low.
6. Bladder cancer. This appears as an adverse effect more specifically from pioglitazone. It’s a proposal that stemmed from studies on male rats, but human studies show little to no correlation. This possible correlation, however, is thought to be from long term exposure. From your bladder cells being repeatedly exposed to the pioglitazone metabolites.
7. Bone fracture. The stem cells inside bone marrow can either become adipocytes or osteoblasts. By activation of the PPAR-γ receptor you probably understand which kind of cell is chosen. Overtime if your body starts disproportionally making more marrow adipocytes at the expense of osteoblasts, your bones will weaken. Older women in particular are at the highest risk of this adverse effect.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5651605/

Now if you look at all of these adverse affects, you can clearly see that practically ALL of these are from oral intake. I don’t think applying a topical formulation of one of these TZDs is gonna travel all the way to your kidneys…fuck up your sodium excretion…travel to your retina…blind you permanently..so on and so forth.

The idea of topical TZDs is so convenient, that’s it’s literally been experimented with in the past. Meet Topokine Therepeutics. This biotech company experimented with creating topical rosiglitazone and other tzds in the past, as a product for local fat optimization.

https://patentimages.storage.googleapis.com/54/17/e8/fe6c9c5256bbc3/US8883834.pdf?utm

This document outlines their project. On page 33 you can see the results of the experiments they conducted. They experimented with creating formulations with different kinds of thiazolidinediones, including formulations containing 0.1% and 0.3% rosiglitazone. Incredible results were revealed.

In order to create a topical formulation for this, it’s important that it reaches the subcutaneous layer without being systemically absorbed through your bloodstream. That’s probably the main reason why the project was abandoned, the critics of it didn’t think the public would respond nicely to this idea of using a diabetes medication topically. Because of the network of capillaries in the skin's dermis. Topokine Therapeutics addressed this as the “sink condition”.

View attachment 388582

It’s a pharmacological term describing how specific tissues act as “sinks”, transporting the medication into the bloodstream instead of the target site. This is a prevalent effect in subcutaneous drug delivery, let alone pharmacokinetics in general.

Drug molecules will naturally move from high concentration to low concentration, so the capillaries in the dermis offer a lower concentration for the molecules to gravitate towards, which eventually lead to them entering your bloodstream. Thiazolidinediones are lipophilic, so they are literally in favor of penetrating deeply and reaching the bloodstream. They aimed to make something that could penetrate the skin enough to enter the subq layer, but WITHOUT diffusion into the capillaries.

View attachment 388583

What’s so damn splendid about their creation is how it somehow counters the sink effect. Somehow implanting the medication into the subq layer with negligible amounts of systemic exposure. The patents proved this by running multiple drug tests including Cmax, AUC, LC-MS/MS. They collected blood samples from all of the pigs they tested on. They concluded that peak plasma concentrations were about 3400 and 1300 FOLD LOWER than for oral therapy. Over the 42 day dosing period only that smidgen made it into the bloodstream.

It’s unclear how the ingredients work together to deliver the drug into the fat layer with minimal systemic exposure. But I think I figured out the mental gymnastics. If you zoom into the molecular picture, rosiglitazone is ~357 Da. According to the Dalton rule this can easily penetrate the skin barrier, and you would think with a weight like this it could easily get swelled up by the capillaries. But the ingredients all work together to swarm down the skin barrier so fast the capillary network doesn’t even see them coming. The ethanol evaporates onto your skin whilst altering the stratum corneum. After this layer is left behind, the concentrations of the other ingredients skyrocket since over 65% of the product has dissipated. The remaining propylene glycol can barely hold the drug so the liquid becomes supersaturated. The drug gets blasted through the loose dermis. The capillaries in the skin are not fenestrated. They’re continuous, and once the drug molecules reach these capillaries they ambush the microscopic transport pores. The idle lipophilic molecules immediately passively diffuse into the subcutaneous layer beneath the dermis, and they stay there.

After 42 days of using 0.3mL on 6 different treatment areas, a mean of a whopping 48% fat increase was noticed. Four mini pigs (the animal with the most similar skin to humans) were tested on.

View attachment 388584

I’m gonna shout this again. The mean fat thickness over placebo is a 48% INCREASE.

Now for the million dollar question, what’s the recipe for this topical formulation that they used?

View attachment 388585

Each one of these ingredients (aside from our tzd) are fundamentally safe for topical human use and are common ingredients in the skincare industry.

You can substitute the rosiglitazone with other thiazolidiones like pioglitazone and experiment around, but if you take the time to read the patents papers, pioglitazone in particular doesn’t give the most outstanding results. It still worked, but not as well as rosiglitazone. There’s other glitazones as well like ciglitazone. Lobeglitazone is the one that’s even stronger than rosiglitazone, and patients only take 0.5 mg of it. There’s just so many others under this drug class that people could experiment with.

Formulation ingredients:
Rosiglitazone
This is the TZD we’d be using, the patent is never actually clear on what form of rosiglitazone they used. But according to the context clues I’d say that the experiment did NOT use the malleate version (rosiglitazone malleate is the kind they use in the oral tablets), and they probably just used regular free base rosiglitazone. If they had used any specific version they would have specified. Looks like you can find rosiglitazone on this marketplace, but make SURE what you get is in free base form. https://www.echemi.com/searchGoods/temppid160705010001-rosiglitazone.html
https://www.glentham.com/en/products/product/GP6434/?utm_
https://www.chemimpex.com/products/...-8Kb6Rnp20YfaLU3IthxlarNo-QtVinjNxU4rMzQ9sfzi

Alpha-tocopherol (aka vitamin E)
is an antioxidant so that the gel doesn’t go bad. It’s unclear whether they used synthetic or natural in their experiments..but they do list exemplary antioxidants that are synthetic so I don’t think it matters. I found this gem for cheap, and it’s pure free tocopherol. You only need a very miniscule amount of this for it to do its job. Pure dl-alpha-tocopherol has a density of roughly 0.95 grams per milliliter, so you’d only need .0021ml of this stuff in the 100g formulation. Now because of the fact that that’s practically fucking impossible to measure, you’re gonna do the stock solution method to measure it (I’ll elaborate in the “how to” section)
https://www.makingcosmetics.com/VIT-VITE-01.html?lang=en_US

Anhydrous ethanol (ethanol with practically no water)
will help the product penetrate the stratum corneum as I said before. The kind they used was very pure, look for 200 proof non denatured ethanol. You’d use about 86.3mL of this per 100g of final product.
https://www.usalab.com/usa-lab-200-proof-ethanol-usp-99-97-1gal-5gal-55gal-270gal-excise-tax-included/?

As for the propylene glycol, you want very pure medical grade product asw. You’d add 26.06ml of this into the 100g batch.
https://www.walmart.com/ip/Propylen...-non-gmo-premium-natural-pure-32-oz/829649994

3.37ml of oleic acid in 100g batch
https://www.ebay.com/itm/2222473408...gdN5wKS3mgfbW8c4gSl0xzSvG3jSWrInknpDTQZPmDL-o

For the Klucel/HPC,
they don’t specify what grade they used. But from context clues, they most likely used Klucel® HF. (Edit: I don’t know why the fuck I said context clues, it literally says HF.) The formulation is supposed to be a gel, and if you added only 1g of something like EF/LF in a 10g batch, that would barely change the consistency at all. This should be weighed on a scale (favorably a four place balance, but that’s pretty expensive shit that I wouldn’t assume many of you have. A three place balance is aight instead)

https://www.kremer-pigmente.com/en/shop/mediums-binders-glues/63713-klucel-hf-pharm.html

Spoiler: How you’d actually cook this up

You’re going to want one syringe per ingredient. Cross contamination is a no no, getting everything precise is crucial. Get a nice big pack of syringes. https://www.ebay.com/itm/387000288770

https://www.premiumvials.com/30-pac...Qp_gX7QNZmwUChkbjH3VwgjSt4VcmSh_YAsvW342vvcDy

For this mixture, an amber glass mason jar works well. Since amber glass absorbs all kinds of light wavelengths. Keep that lid next to you at all times. Your mixture needs minimal exposure to air.
https://www.premiumvials.com/2-oz-a...127&gbraid=0AAAAADpaBkCcgWGovPzMQy67RBWzvL57P

Wear a mask when handling the rosiglitazone powder. You don’t want to inhale it.

The anhydrous ethanol is an ingredient you shouldn’t fuck around with, it should have MINIMAL exposure to air. The air will ruin it. The ethanol is so pure so if left exposed for the air for too long it can absorb water from the air, which fucks up your ratios and the entire point of it being “anhydrous”. Never ever leave the cap off of your ethanol bottle, it will spoil the whole thing.

And it just so happens to be the first product topokine therepeutics adds to the batch. So you should draw up all your other liquid ingredients beforehand so this entire mixing process goes as fast as possible.

You need only 2.1 µL of vitamin E. In order to measure this, you’re gonna make a 1:100 stock solution including propylene glycol. Add 9.9ml of propylene glycol and 0.1ml of vitamin e in a small vial. Now every 1 ml of the liquid has 0.01ml of vitamin E. You’d deduct 0.21ml of this stock solution with a syringe to get .0021ml of vitamin E.

Now because most of that stock solution is propylene glycol, you’re just gonna subtract that amount from your main batch to be precise and avoid any mishaps in your ratios. So you’d go 26.06ml - 0.21ml for your main propylene glycol measurement.

The first ingredient to add to the solvent beaker is 86.3ml of Anhydrous ethanol. Then after that, you’d immediately add your 25.85ml of propylene glycol, 3.37ml of oleic acid, and 0.21ml of stock solution (the vitamin E). Immediately cover your batch with the lid after adding all these. Also IMMEDIATELY put the caps back on the bottles of your chemicals, ESPECIALLY the ethanol.

Now it’s time for you to weigh out the powders. You can take your time for this part since your mixture is covered.

What sucks is you’d ideally want to use a 4 place balance to measure these out, but not a single one of those is under 100 bucks. So a cheaper 3 place scale is usually where you end up. When weighing these out, the scale should be far away from any vents, windows, fans, or anything that could possibly mess with it. Zero the scale out and you can put some weighing paper on it for the powder. Then scoop some tiny amounts of the rosiglitazone powder onto the scale. When the scale finally reads 1g, carefully funnel the weighing paper and add the powder to the batch. Stir until the liquid is clear, and then cover it back up again.

Now for the Klucel, you’re gonna weigh out 1g of it the same way you did rosiglitazone. Go over to the scale and weigh 1g. It has a relatively low bulk density, so don’t be surprised if 1g looks bulkier than it should. Dispersing this powder is incredibly important, as this is the ingredient that gives your gel its viscosity. You’re gonna uncover your batch and start whisking that shit away with a stirring rod like there’s no tomorrow. While you stir your mixture in this volatile manner, sprinkle in the Klucel. You want to scatter each dry particle of the powder throughout your mixture. Once the Klucel is all the way sprinkled in, SLOW your stirring speed to avoid bubbles. This entire dispursement should be 1-2 minutes, after that cover your shit up immediately. Remember, ethanol is a ticking time bomb.

Now, you let your batch sit. Store it in a dark cabinet away from any light (thiazolidiones are light sensitive). After 2 hours you can take it out, take the lid off and stir it for another minute. This will be the final time you stir it for the day. Then put it back and let it sit overnight.

The next day, you can begin to use your gel. It shouldn’t look cloudy/grainy, but instead uniform and smooth.

It should be stored long term in a pitch black pantry/cabinet, at a stable room temp.
View attachment 388600

Potential flaw/s: I’m sure when most of us think of volufiline, we think of something to fill recessed infras. A potential flaw with that is that the skin around the eyes is the part of the body with the thinnest skin. With how well the topical gel works, its permeability is what should make you feel weary about applying it there. A viable workaround for this would be to create an alternative formulation with less penetration enhancers.

You wouldn’t want this gel to touch your actual lower eyelid either (aegyo sal), or else you’d be giving yourself steatoblepharon. Applying a pea sized amount of the gel and rubbing it in your desired areas whilst putting tape on your lower eyelid (to ensure the gel doesn’t touch it), would be the safer way to go. Not risk free though. However applying this gel to your under eyelid is not going to wind up in the retina (causing muh macular edema). The capillaries under your eyelid don’t flow backwards towards the retina, they take blood away from the eye. What supplies the retina is the central retinal artery, which is way in the back of your eyeball in the optic nerve trunk. The actual risks here concerning applying this to the infras would be a possible increased amount of the drug in your bloodstream (from the network of ocular capillaries close to the surface of the thin skin), and the product working too well in the wrong places.

Applying it to the supras on the other hand is safer (the skin is thicker there), but you’d have to be very careful about the gel migrating or touching your actual upper eyelid. You wouldn’t want to be thickening your actual eyelid, you’d be giving yourself ptosis. A work around to this would be applying the gel right on your eyebrow, and putting tape on your eyelids just in case.

This is all hypothetical I’m not a professional don’t sue me
@Mandy? @ecoli @Histy @LaWi @Arya @Whitepill @foidslayer

can this grow bones

 

[Rololongs]

I’m sure everyone here has heard of volufiline, or other topicals that are marketed to give a lipofilling effect. Go check out @genio thread eviscerating volucope

Guide Volufiline: Why it's Cope and What to Do Instead

Jul 2, 2026

Volufiline: Why it's Cope and What to...​

• genio
• Replies: 40
• Forum: Looksmaxxing

• 
• 
• 

His thread mentions Rosiglitazone under non surgical procedures, which is something that’s garnered a bit of attention from this community. Rosiglitazoney is a potent PPAR-γ agonist belonging to the drug class of thiazolidiones, and it is a hidden gem for localized fat growth. I mean that literally. It was a potential product that was buried.


Mechanism

View attachment 388571

I’m sure most of us are familiar with what type 2 diabetes is. When your bodies insulin receptors become desensitized, making it harder to store energy appropriately. Because of this, people with type 2 often have higher levels of insulin since their body is trying to fight their resistance. But this obviously doesn’t last them forever, and stresses the beta cells in their pancreas to death. Well oral TZDs (Thiazolidinediones), like rosiglitazone and pioglitazone aim to work around this issue by targeting the PPAR-γ receptor (peroxisome proliferator-activated receptor gamma) which sits in the nucleus inside the cells. It indirectly helps with clearing the bloodstream of glucose/storing it, adipogenesis, and insulin sensitivity. To be more specific, when the receptor is activated, it binds and creates a heterodimer with RXR to transcribe genes.
Its change in gene expression causes more GLUT4 production which is the transporter that allows glucose to enter the cell. Hence, higher insulin sensitivity and less blood sugar. It also promotes differentiation of preadipocytes into mature adipocytes. Rosiglitazone (Avandia) is administered with a starting dose of 4mg, but if patients respond inadequately follow 8-12 weeks of treatment they can bump their dosage up to 8mg.

We don’t have tons of clinical studies conducting research on applying this in topical form onto humans, since it was created as a diabetes medication. But there are still studies about its topical use here and there that suggest its healing properties:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12023181/
https://pmc.ncbi.nlm.nih.gov/articles/PMC3733781/
https://www.cell.com/molecular-therapy-family/advances/fulltext/S3117-387X(26)00067-4
https://www.sciencedirect.com/science/article/pii/S0022202X15371050

Rosiglitazone and pioglitazone are the two main thiazolidiones that have been investigated as topicals. But there are still plenty of others under that drug class that have been researched but less extensively (ex: ciglitazone, troglitazone).

Risks
Let’s talk about practically EVERY SINGLE risk related to TZDs. Let’s keep in mind that most of these risks are minimized in the form of topical use.

1. Edema. If you’re unaware of what this is, it’s the medical term for swelling from excess fluids being trapped in your bodies tissues. The PPAR-γ receptor is not only present in regular adipocytes but it is also in kidney cells, particularly in the collecting ducts and distal tubules. The goal of the DSCT is to reabsorb more sodium chloride and water. The hormones aldosterone and ADH can act upon this. ADH will talk to dct increase water reabsorption , aldosterone will increase salt reabsorption. So remaining sodium winds up in the collecting duct to be reabsorbed. I’ll remind you of the inverse relationship between sodium and potassium- sodium pulls fluid outside of cells while potassium stores it inside. Activation of the PPAR-γ receptor causes more sodium reabsorption back into the bloodstream, and since water moves by osmosis more water is also reabsorbed. This causes a big bloated mess, and the fluid leaks into surrounding tissues. It’s specifically called peripheral edema, but there’s also other kinds of edema that have been reported. Macular edema is swelling in the macula, causing vision changes. Some of you might be aware of the fact that this has been reported before as a rare adverse affect from TZDs. But we have to keep in mind that people who have blood retinal barrier dysfunction (from their diabetes) are the ones who are at higher risk of this. Having diabetes alone usually causes a certain degree of damage to that barrier, so in most reports it’s very possible that the TZD just exacerbated a pre existing issue, and I think most of us on here are NOT diabetic. Most of the reports of macular edema even wind up being reversible, so their vision goes back to normal after stopping. This is because edema is only fluid buildup, it’s not necessarily causing permanent damage to the surrounding cells, it’s just disarranging them out of place. Now how do we work around this..? Well we’re gonna be making a TOPICAL formulation. Meaning it’s only going to work locally. If you look at all of these cases of edema, it’s from diabetics who frequently take oral TZDs as well as usually taking insulin alongside it.
2. Heart problems. If you read what I said for edema, it’s practically the same cause. The body starts to gain more fluid retention since more sodium and water get reabsorbed back into the bloodstream. More fluid starts to circulate through your bloodstream, so because of that your heart will have a heavier preload. It will have to pump a larger volume of blood. That’s why TZDs can worsen a heart that’s already weakened, or even cause new problems since overload that’s very prolonged (months to years) will stress your heart. Now how would we work around this? Well we wouldn’t even have to. A topical formation isn’t gonna give you heart failure as it only works locally
3. Increased cholesterol. Both rosiglitazone and pioglitazone lower triglycerides and increase HDL levels..but apparently rosiglitazone can increase LDL, and so can pioglitazone but to lower extents. If your body builds up too much of the bad cholesterol, it builds up in the walls of your arteries. Causing dangerous plaque to form, which narrows the artery. It can build up in very important arteries that supply blood flow to the heart and even the brain.
4. Hypertension. This is just more of the same stuff. Hypertension is the word for chronically high blood pressure, which can damage your heart and kidneys. Because of the fact that oral TZDs can cause more water and sodium reabsorption into the circulation, your blood volume will increase.
5. Hypoglycemia. This actually rarely happens when only on TZDs, but hypoglycemia is when your blood glucose levels are too low. After activating the PPAR-γ receptor, your cells will become more responsive towards insulin. Sometimes this piece alone is enough to knock someone’s blood sugar levels too low.
6. Bladder cancer. This appears as an adverse effect more specifically from pioglitazone. It’s a proposal that stemmed from studies on male rats, but human studies show little to no correlation. This possible correlation, however, is thought to be from long term exposure. From your bladder cells being repeatedly exposed to the pioglitazone metabolites.
7. Bone fracture. The stem cells inside bone marrow can either become adipocytes or osteoblasts. By activation of the PPAR-γ receptor you probably understand which kind of cell is chosen. Overtime if your body starts disproportionally making more marrow adipocytes at the expense of osteoblasts, your bones will weaken. Older women in particular are at the highest risk of this adverse effect.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5651605/

Now if you look at all of these adverse affects, you can clearly see that practically ALL of these are from oral intake. I don’t think applying a topical formulation of one of these TZDs is gonna travel all the way to your kidneys…fuck up your sodium excretion…travel to your retina…blind you permanently..so on and so forth.

The idea of topical TZDs is so convenient, that’s it’s literally been experimented with in the past. Meet Topokine Therepeutics. This biotech company experimented with creating topical rosiglitazone and other tzds in the past, as a product for local fat optimization.

https://patentimages.storage.googleapis.com/54/17/e8/fe6c9c5256bbc3/US8883834.pdf?utm

This document outlines their project. On page 33 you can see the results of the experiments they conducted. They experimented with creating formulations with different kinds of thiazolidinediones, including formulations containing 0.1% and 0.3% rosiglitazone. Incredible results were revealed.

In order to create a topical formulation for this, it’s important that it reaches the subcutaneous layer without being systemically absorbed through your bloodstream. That’s probably the main reason why the project was abandoned, the critics of it didn’t think the public would respond nicely to this idea of using a diabetes medication topically. Because of the network of capillaries in the skin's dermis. Topokine Therapeutics addressed this as the “sink condition”.

View attachment 388582

It’s a pharmacological term describing how specific tissues act as “sinks”, transporting the medication into the bloodstream instead of the target site. This is a prevalent effect in subcutaneous drug delivery, let alone pharmacokinetics in general.

Drug molecules will naturally move from high concentration to low concentration, so the capillaries in the dermis offer a lower concentration for the molecules to gravitate towards, which eventually lead to them entering your bloodstream. Thiazolidinediones are lipophilic, so they are literally in favor of penetrating deeply and reaching the bloodstream. They aimed to make something that could penetrate the skin enough to enter the subq layer, but WITHOUT diffusion into the capillaries.

View attachment 388583

What’s so damn splendid about their creation is how it somehow counters the sink effect. Somehow implanting the medication into the subq layer with negligible amounts of systemic exposure. The patents proved this by running multiple drug tests including Cmax, AUC, LC-MS/MS. They collected blood samples from all of the pigs they tested on. They concluded that peak plasma concentrations were about 3400 and 1300 FOLD LOWER than for oral therapy. Over the 42 day dosing period only that smidgen made it into the bloodstream.

It’s unclear how the ingredients work together to deliver the drug into the fat layer with minimal systemic exposure. But I think I figured out the mental gymnastics. If you zoom into the molecular picture, rosiglitazone is ~357 Da. According to the Dalton rule this can easily penetrate the skin barrier, and you would think with a weight like this it could easily get swelled up by the capillaries. But the ingredients all work together to swarm down the skin barrier so fast the capillary network doesn’t even see them coming. The ethanol evaporates onto your skin whilst altering the stratum corneum. After this layer is left behind, the concentrations of the other ingredients skyrocket since over 65% of the product has dissipated. The remaining propylene glycol can barely hold the drug so the liquid becomes supersaturated. The drug gets blasted through the loose dermis. The capillaries in the skin are not fenestrated. They’re continuous, and once the drug molecules reach these capillaries they ambush the microscopic transport pores. The idle lipophilic molecules immediately passively diffuse into the subcutaneous layer beneath the dermis, and they stay there.

After 42 days of using 0.3mL on 6 different treatment areas, a mean of a whopping 48% fat increase was noticed. Four mini pigs (the animal with the most similar skin to humans) were tested on.

View attachment 388584

I’m gonna shout this again. The mean fat thickness over placebo is a 48% INCREASE.

Now for the million dollar question, what’s the recipe for this topical formulation that they used?

View attachment 388585

Each one of these ingredients (aside from our tzd) are fundamentally safe for topical human use and are common ingredients in the skincare industry.

You can substitute the rosiglitazone with other thiazolidiones like pioglitazone and experiment around, but if you take the time to read the patents papers, pioglitazone in particular doesn’t give the most outstanding results. It still worked, but not as well as rosiglitazone. There’s other glitazones as well like ciglitazone. Lobeglitazone is the one that’s even stronger than rosiglitazone, and patients only take 0.5 mg of it. There’s just so many others under this drug class that people could experiment with.

Formulation ingredients:
Rosiglitazone
This is the TZD we’d be using, the patent is never actually clear on what form of rosiglitazone they used. But according to the context clues I’d say that the experiment did NOT use the malleate version (rosiglitazone malleate is the kind they use in the oral tablets), and they probably just used regular free base rosiglitazone. If they had used any specific version they would have specified. Looks like you can find rosiglitazone on this marketplace, but make SURE what you get is in free base form. https://www.echemi.com/searchGoods/temppid160705010001-rosiglitazone.html
https://www.glentham.com/en/products/product/GP6434/?utm_
https://www.chemimpex.com/products/...-8Kb6Rnp20YfaLU3IthxlarNo-QtVinjNxU4rMzQ9sfzi

Alpha-tocopherol (aka vitamin E)
is an antioxidant so that the gel doesn’t go bad. It’s unclear whether they used synthetic or natural in their experiments..but they do list exemplary antioxidants that are synthetic so I don’t think it matters. I found this gem for cheap, and it’s pure free tocopherol. You only need a very miniscule amount of this for it to do its job. Pure dl-alpha-tocopherol has a density of roughly 0.95 grams per milliliter, so you’d only need .0021ml of this stuff in the 100g formulation. Now because of the fact that that’s practically fucking impossible to measure, you’re gonna do the stock solution method to measure it (I’ll elaborate in the “how to” section)
https://www.makingcosmetics.com/VIT-VITE-01.html?lang=en_US

Anhydrous ethanol (ethanol with practically no water)
will help the product penetrate the stratum corneum as I said before. The kind they used was very pure, look for 200 proof non denatured ethanol. You’d use about 86.3mL of this per 100g of final product.
https://www.usalab.com/usa-lab-200-proof-ethanol-usp-99-97-1gal-5gal-55gal-270gal-excise-tax-included/?

As for the propylene glycol, you want very pure medical grade product asw. You’d add 26.06ml of this into the 100g batch.
https://www.walmart.com/ip/Propylen...-non-gmo-premium-natural-pure-32-oz/829649994

3.37ml of oleic acid in 100g batch
https://www.ebay.com/itm/2222473408...gdN5wKS3mgfbW8c4gSl0xzSvG3jSWrInknpDTQZPmDL-o

For the Klucel/HPC,
they don’t specify what grade they used. But from context clues, they most likely used Klucel® HF. (Edit: I don’t know why the fuck I said context clues, it literally says HF.) The formulation is supposed to be a gel, and if you added only 1g of something like EF/LF in a 10g batch, that would barely change the consistency at all. This should be weighed on a scale (favorably a four place balance, but that’s pretty expensive shit that I wouldn’t assume many of you have. A three place balance is aight instead)

https://www.kremer-pigmente.com/en/shop/mediums-binders-glues/63713-klucel-hf-pharm.html

Spoiler: How you’d actually cook this up

You’re going to want one syringe per ingredient. Cross contamination is a no no, getting everything precise is crucial. Get a nice big pack of syringes. https://www.ebay.com/itm/387000288770

https://www.premiumvials.com/30-pac...Qp_gX7QNZmwUChkbjH3VwgjSt4VcmSh_YAsvW342vvcDy

For this mixture, an amber glass mason jar works well. Since amber glass absorbs all kinds of light wavelengths. Keep that lid next to you at all times. Your mixture needs minimal exposure to air.
https://www.premiumvials.com/2-oz-a...127&gbraid=0AAAAADpaBkCcgWGovPzMQy67RBWzvL57P

Wear a mask when handling the rosiglitazone powder. You don’t want to inhale it.

The anhydrous ethanol is an ingredient you shouldn’t fuck around with, it should have MINIMAL exposure to air. The air will ruin it. The ethanol is so pure so if left exposed for the air for too long it can absorb water from the air, which fucks up your ratios and the entire point of it being “anhydrous”. Never ever leave the cap off of your ethanol bottle, it will spoil the whole thing.

And it just so happens to be the first product topokine therepeutics adds to the batch. So you should draw up all your other liquid ingredients beforehand so this entire mixing process goes as fast as possible.

You need only 2.1 µL of vitamin E. In order to measure this, you’re gonna make a 1:100 stock solution including propylene glycol. Add 9.9ml of propylene glycol and 0.1ml of vitamin e in a small vial. Now every 1 ml of the liquid has 0.01ml of vitamin E. You’d deduct 0.21ml of this stock solution with a syringe to get .0021ml of vitamin E.

Now because most of that stock solution is propylene glycol, you’re just gonna subtract that amount from your main batch to be precise and avoid any mishaps in your ratios. So you’d go 26.06ml - 0.21ml for your main propylene glycol measurement.

The first ingredient to add to the solvent beaker is 86.3ml of Anhydrous ethanol. Then after that, you’d immediately add your 25.85ml of propylene glycol, 3.37ml of oleic acid, and 0.21ml of stock solution (the vitamin E). Immediately cover your batch with the lid after adding all these. Also IMMEDIATELY put the caps back on the bottles of your chemicals, ESPECIALLY the ethanol.

Now it’s time for you to weigh out the powders. You can take your time for this part since your mixture is covered.

What sucks is you’d ideally want to use a 4 place balance to measure these out, but not a single one of those is under 100 bucks. So a cheaper 3 place scale is usually where you end up. When weighing these out, the scale should be far away from any vents, windows, fans, or anything that could possibly mess with it. Zero the scale out and you can put some weighing paper on it for the powder. Then scoop some tiny amounts of the rosiglitazone powder onto the scale. When the scale finally reads 1g, carefully funnel the weighing paper and add the powder to the batch. Stir until the liquid is clear, and then cover it back up again.

Now for the Klucel, you’re gonna weigh out 1g of it the same way you did rosiglitazone. Go over to the scale and weigh 1g. It has a relatively low bulk density, so don’t be surprised if 1g looks bulkier than it should. Dispersing this powder is incredibly important, as this is the ingredient that gives your gel its viscosity. You’re gonna uncover your batch and start whisking that shit away with a stirring rod like there’s no tomorrow. While you stir your mixture in this volatile manner, sprinkle in the Klucel. You want to scatter each dry particle of the powder throughout your mixture. Once the Klucel is all the way sprinkled in, SLOW your stirring speed to avoid bubbles. This entire dispursement should be 1-2 minutes, after that cover your shit up immediately. Remember, ethanol is a ticking time bomb.

Now, you let your batch sit. Store it in a dark cabinet away from any light (thiazolidiones are light sensitive). After 2 hours you can take it out, take the lid off and stir it for another minute. This will be the final time you stir it for the day. Then put it back and let it sit overnight.

The next day, you can begin to use your gel. It shouldn’t look cloudy/grainy, but instead uniform and smooth.

It should be stored long term in a pitch black pantry/cabinet, at a stable room temp.
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Potential flaw/s: I’m sure when most of us think of volufiline, we think of something to fill recessed infras. A potential flaw with that is that the skin around the eyes is the part of the body with the thinnest skin. With how well the topical gel works, its permeability is what should make you feel weary about applying it there. A viable workaround for this would be to create an alternative formulation with less penetration enhancers.

You wouldn’t want this gel to touch your actual lower eyelid either (aegyo sal), or else you’d be giving yourself steatoblepharon. Applying a pea sized amount of the gel and rubbing it in your desired areas whilst putting tape on your lower eyelid (to ensure the gel doesn’t touch it), would be the safer way to go. Not risk free though. However applying this gel to your under eyelid is not going to wind up in the retina (causing muh macular edema). The capillaries under your eyelid don’t flow backwards towards the retina, they take blood away from the eye. What supplies the retina is the central retinal artery, which is way in the back of your eyeball in the optic nerve trunk. The actual risks here concerning applying this to the infras would be a possible increased amount of the drug in your bloodstream (from the network of ocular capillaries close to the surface of the thin skin), and the product working too well in the wrong places.

Applying it to the supras on the other hand is safer (the skin is thicker there), but you’d have to be very careful about the gel migrating or touching your actual upper eyelid. You wouldn’t want to be thickening your actual eyelid, you’d be giving yourself ptosis. A work around to this would be applying the gel right on your eyebrow, and putting tape on your eyelids just in case.

This is all hypothetical I’m not a professional don’t sue me
@Mandy? @ecoli @Histy @LaWi @Arya @Whitepill @foidslayer

Your so smart

 

[otter]

Do you have an opinion on SDA 40B 200 proof cosmetic grade ethanol instead of USP? I already have some.

 

[giga.mia]

How's the eye stuff going btw

I’m such a lazy bag of shit I keep postponing my filler, I will surely deal with all this after my filler

 

[giga.mia]

Do you have an opinion on SDA 40B 200 proof cosmetic grade ethanol instead of USP? I already have some.

In my eyes they’re the same, I think we should comprise a formula that doesn’t use an ingredient like ethanol cause of how damaging it can be
But in the end it depends on the concentration your using, if it’s negligible amounts it’s fine

 

[giga.mia]

Wow this is fascinating.

I wonder if I used this during a caloric deficit? Would facial fat grow anyways or grow new but empty fat cells that would inflate in the future?

This is definitely interesting to think about, I’d advise against it to be honest
I read somewhere that rosi causes browning of fat cells so you wouldn’t want to risk loosing the new gains, they’ll turn into white a few weeks after application

I think topekine used roglitzione because pioglitzione converts to an active metabolite in the liver that last 3 to 4 times longer than poglitzione itself meaning onger systemic effects.

Yes it’s more potent, but with that we need to be extra careful to not let it go systemic

One may have to be careful so topical retinoids don't penetrate skin super deeply with this and get into fat pads. Retinoids block pre adipocyte differentiation and downregulate glut4, the opposite of what we want.

Yup, luckily I don’t think there’s any retinoids in the formulas we’ve been discussing

Two other possible ingredients to add.

Myristl nicotinamide is an ingredient common in skin barrier repair creams. It's a fat soluble ester that slowly releases niacin. The niacin will block HSL to prevent fat loss when calories aren't high

Estradiol upregulates adrenergic a2 receptors that puts a brake on HSL triggered by catecholamines.

Roglitzione increases glut4 proteins which bring glucose into fat cells when the glut4 is triggered by insulin. Estradiol is a lesser trigger of glut4 release too.

These all sound like nice products, I’ve revamped the formula into something else a while ago and I’m curious to see what you think of this, it’s purpose is to be more gentle on the skin

Unfortunately if estradiol goes systemic you might do something scandalizing and regrettable like order a subscription to the Hallmark channel. That's my 9th greatest fear.