A Question for the RU experts - Nanoemulsion

[Guildenstern]

Hey guys.

So i know a chemist who has access to liposome nanobodies and says he can load a topical with 0.8% RU58841. He claims it boosts the absorption by 5-10 times and indeed i have found enough literature to support this claim.
However, ever since users reported heart-problems (and sometimes brain-fog) i am a little anxious to use the drug.
I researched into the topic of systemic absorption of transdermally applied nanoemulsions, but found little.


this paper is from berlin and was done on SLNs and RU-myristate (some of you might be familiar with it)

http://www.ingentaconnect.com/content/govi/pharmaz/2005/00000060/00000001/art00002?crawler=true

but this paper:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055113/

clearly states that there is a certain amount of toxicity although cosmetic companies claiming otherwise (point 7)


Does anyone of you have any scientific paper about the systemic absorption of compounds that were applied topically via nanobodies? Is it safe? :O

Thanks in advance!

[allTheGoodNamesAreTaken]

If its 5x-10x better then why not start with 1/5th - 1/10th the normal amount and slowly increase?

[jamesst11]

Hey guys.

So i know a chemist who has access to liposome nanobodies and says he can load a topical with 0.8% RU58841. He claims it boosts the absorption by 5-10 times and indeed i have found enough literature to support this claim.
However, ever since users reported heart-problems (and sometimes brain-fog) i am a little anxious to use the drug.
I researched into the topic of systemic absorption of transdermally applied nanoemulsions, but found little.


this paper is from berlin and was done on SLNs and RU-myristate (some of you might be familiar with it)

http://www.ingentaconnect.com/content/govi/pharmaz/2005/00000060/00000001/art00002?crawler=true

but this paper:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055113/

clearly states that there is a certain amount of toxicity although cosmetic companies claiming otherwise (point 7)


Does anyone of you have any scientific paper about the systemic absorption of compounds that were applied topically via nanobodies? Is it safe? :O

Thanks in advance!

Is absorption really an issue? People are reporting systemic side effects with using RU. I don't think delivery is really an issue, especially with microneedling. No?

[Guildenstern]

If its 5x-10x better then why not start with 1/5th - 1/10th the normal amount and slowly increase?

That was the plan. Apparently, 0.8% is the maximum loading you can achieve (at least according to this man), which would mean that it appoximately equals 5% RU in Eth/PG or K&B solution.
I don't question the penetration-abilities of the emulsion, but when it enhances skin penetration by that degree, wouldn't it be likely it also boosts systemic absorption by a fair amount?

The Solution in question is just standardized lipid nanoparticles. But there's a hundred dermatology papers regarding this topic. And all claim different things.

Sometimes the solution doesn't perpetrate the dermis and just acts as a local distributor for the loaded drug. Other times they use transdermally applied drugs for diabetic treatment, which - in my view - would imply that it does indeed penetrate the dermis and hit the bloodstream.

However, i specifically wanted to use nanoparticles to negate any systemic effect. But i am very confused whether or not this is actually the case with nanoemulsions. Is anyone read well enough to shed some light on this for me?

I guess it's already a boon that you just have to use 8 mg of RU instead of using 50 mg, to achieve more or less the same effect if the penetration is actually increased by that amount over alcohol-solutions. But 8 mg of RU - made harder to biodegrade - is still a thing i guess. Maybe i'm just too anxious. Still - anybody got an idea?

[Guildenstern]

I just found that the link partially answers the question, however, can anyone confirm this for me?

"
2.4. Cellular toxicity
Neither RU 58841 nor RUM (106–104 M) reduced cell
viability in any investigated cell type (dermal papilla cells
were not tested for RU 58841 and RUM 104 M). Therefore
underestimation of cutaneous metabolism due to cellular
toxicity is excluded.

2.5. Permeation experiments
Because of varying and dissatisfying extraction rates of
RUM from FCS containing acceptor fluids drug permeation
had to be followed after esteratic cleavage via RU
58841 detection. Yet, neither RUM nor RU 58841 was
detected in any type of acceptor fluid. This holds true
with all preparations tested (0.1% and 1% cream preparation,
0.1% nanoemulsion, and 0.1% SLN) and both with
full thickness porcine skin and with reconstructed epidermis.
2.6. Characterization of the follicular penetration
To demonstrate follicular penetration, Nil Red labelled
Compritol based SLN (LD50: 153 nm LD95: 484 nm),
Miglyol based nanoemulsion (LD50: 189 nm, LD95:
489 nm) and cream were applied to human scalp skin for
24 h. Fluorescence microscopy revealed an intense fluorescence
within the hair follicles of all investigated preparations.
Fig. 3A demonstrates for Nil Red labelled SLN intense
fluorescence within the hair follicle up to about
200 mm depth. From 400–900 mm skin depth the fluorescence
decreased within the hair follicle but simultaneously
appeared within the sebaceous glands (Fig. 3B). No fluorescence
was detectable in deeper skin layers.
To evaluate if intact SLN may reach the hair follicle 1%
silver sulfadiazine labelled Compritol1 based SLN (LD50:
151 nm, LD95: 543 nm) were applied to porcine skin for
24 h. TEM allowed to detect intact SLN in the deeper
layer of the hair follicle (Fig. 3C).
"

Does this indeed mean that when RUM or RU58841 were applied to the dermis, the following acceptor fluid did not contain any compound? If this was true, it would basically mean, that RU in Nanoemulsion does only penetrate into the skin, but not out of the skin. Could that be true?

[stratowich]

Does anyone of you have any scientific paper about the systemic absorption of compounds that were applied topically via nanobodies?

Could you please clarify what you mean with nanobodies?

[Guildenstern]

Could you please clarify what you mean with nanobodies?

I meant Liquid Lipid Nanoparticles.