Well, if the high peak pulse dose regimen screws up your brain, I am toast.
After almost four months of high dosing, I am going to take a few months’ break to see how my blood panels are after taking rapamycin for a total of about eight months.
Also, I have tried three kinds of “beyond meat burger”, store-bought, Burger King and Carl Junior’s.
I think I’ll have a hot dog tonight.
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FWIW…do I have this right?
I want 1mg per ml of raperymicin in a 1% solution of DMSO.
100mg of rapamycin dissolved in 1ml of DMSO, then 99ml of saline .9%
Your comments?
Are you just replicating rapamune oral solution at 1mg/mL? Trying to mimic the intransal/mouse study? Are you going to experiment with intransal?
Your math seems right.
Dumping 2 mg (assume both nostrils, 100% uptake) into your CNS…still thinking through this dose vs oral systemic/brain levels data and concentration/dose/delivery, and other variables.
To optimize diffusion/uptake, I’m thinking many small volume misting sprays directed immediately against the olfactory nerves vs have any extra liquid in the nose away from the olfactory (zero efficacy, wasted rapamycin). This has bearing on concentration of formulation. Researching advanced nasal misters. (mister will also have to be calibrated)
Will take me some time to figure this out.
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As always @MAC, your posts are mini-master classes on the topic. Great stuff.
There is a device that came out of the labs of some recent MIT graduates a few years ago that is designed to create ultra-fine mists of droplets that get through the skin much better than normal larger droplets.
I’m wondering if this device (which is available for a few hundred dollars) could be used to increase absorption of the medications in an intranasal application (the company originally was started with medical applications in mind) not sure if it would work for rapamycin though, the size of the rapamycin molecule is on the large size: Sirolimus is 914.172 g/mol
From a Biohacker perspective, it seems like it would be easy to use the small containers that you can purchase from the company, repurposed with sirolimus solution and used for our purposes… seems like something to investigate more. I’ve started the analysis and have read up quite a bit…
Details on the device (which is designed for skin use, but seems like it might work for nasal applications, though you may not want it going into the lungs…?:
The Novopyxis device, known as Droplette, can be loaded with medications, from painkillers to antibiotics. Instead of coalescing into puddles on the skin’s surface, the tiny droplets that stream from the device remain separate and sneak through pores, ferrying drug molecules into the skin, the company says.
Three key innovations make this device technically novel and tailored specifically for both field and lab use: (1) The combination of the piezo and pump to generate sub-micron drug-loaded droplets that penetrate cells, skin, and soft tissue to effectively deliver a range of large molecules, proteins, and nucleic acids. (2) Their assembly in a modular manner which enables portability, safe sterilization, and ejection without direct device-surface contact or significant force, allowing for improved safety and ease of use in both research and clinical settings. (3) The integration of a single-use, sterile cartridge that contains a therapeutic formulation and allows easy integration of a large number of molecules. The platform has broad applications across multiple fields, such as delivery of drugs for inflammatory skin diseases, antibiotics for skin infections, and gene delivery for gene therapy and biomedical research.
Droplette Patent Description:
Droplette is a unique consumer skin care system that transforms ingredient serums into an ultra-fine micro-droplet mist that painlessly absorbs up to 20-times deeper into the skin than topical serum application. Droplette technology heals from deep inside the skin, not outside on the surface of it, without requiring painful needles or harsh chemicals.
Stories on the company:
Podcast Interview with Founders of Droplet
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Where is it available?
But again, I have no idea if it works in the intranasal drug delivery application. But I’m also wondering if we could hack this for delivering sirolimus into the skin (hands, face, etc.) or scalp, or even oral/gum applications also…
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@RapAdmin thanks for the references, I was thinking of something advanced misters per these links. Can any of these be mechanically repurposed for targeted delivery to the olfactory nerve? Or an advanced off the shelf intranasal might suffice. Although they talk about “small molecule” limitations, the key for intransal to work with Rapamycin is the DSMO (although the mouse study used apparently off the shelf Rapamune).
From paper, “50% of the rodent nasal cavity is covered in olfactory epithelia, compared to <5% in humans”. Mice might have a different olfactory BBB nerve structure, allowing for this simpler formulation. Clearly it worked but not translatable to human.
DSMO will carry the Rapamycin through the tight junctions, already documented science in the literature with much larger dalton molecules.
This is just an engineering and dosing problem now.
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Everyone is think out / making it more difficult than what is it is.
My only issue righi now is acquiring rapamycin power analysis >99%{and NOT from China]
I have a Skunk Works.
That is sort of a solvable problem … if you have a friend at a bio / chem lab or academic dept. you could order from Sigma Aldrich or equivalent lab supplies company:
But cost is high for therapeutic levels…
It doesn’t seem like anyone is producing a generic version of the rapamune oral solution:
FWIW
DMSO is almost the perfect solvent, will carry and transport almost any other molecule.
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I am fully aware, am working on this.
200mg of rapamycin powder at less than $100.00. Yes you have to be/have a bio/chem lab, academic dept., Medical research faculty, etc.
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Please share your mouse study translation to human re dosing, qty, delivery to olfactory %, and % of dosed transported (efficiency) into CNS model.
Indeed it is. There’s “hamburger helper” and then there’s “Rapamycin helper”
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Plan on making a copy without the ethanol, propylene glycol, and soya oil.
And taking 1mg up each nostril.
Where are you referencing this…which Rapamycin study?
Sorry, this is not a scientific rationale/model.
But like the hacking spirit!
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Let’s just lie and see if we can get some. (LOL)
Am looking for the black cat in the dark room.
I have posted this before, if you have not read/listen to audiobook review;
“Ignorance: How It Drives Science” by Stuart Firestein
Science is not what you think it is.
It may not be as efficient, but I did find one device on Amazon that should do the trick as it is specifically designed for nasal applications. Looks pretty darn good to me and the price is right.
Curaplex Dart Nasal Atomization Device with 3cc Syringe.
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This is no longer a science issue, we know the fundamentals. What we don’t know is an engineering question, and translation.
Equivalent to where we are with Rapamycin. We know the science, but don’t know the translation. We need to be measuring gene expression and mTOR in human tissues. This is an engineering question…how to do this in humans Vs silent and compliant euthanized mice.
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I like the syringe element for dose control. Thanks for sharing. “Crowd” hacking.