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DMSO.org claims the following:

"[DMSO] is more successful ferrying some drugs, such as morphine sulfate, penicillin, steroids, and cortisone, than others, such as insulin."

All of these drugs that it is said to carry are much larger than a single DMSO molecule.

So what is the general mechanism by which DMSO can bring these relatively high-molecular weight compounds into your body transdermally, where they would not do so otherwise? Does it simply “wrap them up” in a large complex, or does it possibly just complex the portions of the other compound that prevent it from crossing transdermally? What is it about insulin for example that prevents it from being carried through the skin?

A quick internet search will give pages of documents basically saying “this is what it does” but I’ve never found a remotely technical explanation of how this works, particularly for large molecules. That’s what I’m asking here.

NOTE 1: I have never used DMSO medicinally and currently have no intentions of doing so.
NOTE 2: I hope this is not considered a duplicate of this question as the answer is specific to the transport of small molecules.

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Quote taken from the review (1) (and which is also duplicated in Jacob's 2015 "canonical DMSO" book (2, p. 16)):

There is some evidence to suggest that DMSO can increase diffusion through the stratum corneum by disruption of the barrier function. This probably occurs through aprotic interactions with intercellular lipids and may also include reversible distortion of lipid head groups that produce a more permeable packing arrangement. DMSO may also play a role in partitioning as well by forming solvent microenvironments within the tissue that can effectively extract solute from vehicle. Finally, DMSO can have a profound solubilizing effect on less soluble agents in a variety of vehicles, increasing penetration simply by delivering a higher concentration to the membrane barrier.

alongside with extensive molecular modelling by Gurtovenko in 2007 (3) are both suggesting quick pore formation and expansion alongside with the thinning of cellular membranes:

The reported membrane thinning and, in particular, pore formation provide a credible molecular-level explanation of how DMSO promotes permeation of molecules, particularly those of hydrophilic nature, through lipid membranes as observed experimentally.

From what I understand, DMSO paves the way for bigger molecules, such as steroids, making inner skin layers and underlying tissue reversibly accessible, sometimes even on nanoscale level. For the precise mechanism I think it is worth reading through the entire paper (3).

enter image description here

(1) Capriotti, K.; Capriotti, J. A. The Journal of clinical and aesthetic dermatology 2012, 5 (9), 24.
(2) Jacob, S. W.; Jack, C. Dimethyl sulfoxide (DMSO) in trauma and disease; CRC Press, 2015.
(3) Gurtovenko, A. A.; Anwar, J. The Journal of Physical Chemistry B 2007, 111 (35), 10453–10460. DOI 10.1021/jp073113e

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    $\begingroup$ There's a lot of scientific jargon here that is inaccessible for the typical English speaker. How is that helpful? When you boil it down key phrases are "aprotic interactions with ...lipids, "forming solvent microenvironments", "profound solubilizing effect on less soluble agents", "membrane thinning", "pore formation". My sense is that so many possibilities means ideas being thrown about without people really knowing the answer. If so, why use jargon to cover that reality? In laymans terms DMSO is acting as a solvent for the molecules making up the skin, disrupting their function. Am I right? $\endgroup$
    – Tony M
    Commented Mar 17, 2018 at 5:51
  • $\begingroup$ @TonyM If you didn't notice, these are citations from papers, you think authors "cover reality"? Andselisk said it's "making inner skin layers and underlying tissue reversibly accessible" which is quite clear. If you don't understand the jargon then learn more about chemistry and refrain from such comments in the future. $\endgroup$
    – Mithoron
    Commented Jul 8, 2019 at 21:56
  • $\begingroup$ @Mithoron Although I've a lot to learn, I do have a PhD in chemistry have published in and been a reviewer for top journals. Nevertheless, I did not present myself as an expert but instead asked, "Am I right?" When I wrote "cover that reality" I was making reference to the posts here describing the articles rather than the articles themselves. The authors of the original papers should report their observations and explain them in as clear a way as possible; similarly, those trying to explain what they wrote should be also be as clear as possible. Why ask me to refrain from saying that? $\endgroup$
    – Tony M
    Commented Jul 10, 2019 at 8:45

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