Dr_Sister wonders if the failures using DMSO were because they were dissolving the freebase in DMSO rather than a fumarate. Also wondering whether a MAOI would be called for in case the rate of absorption slower that MAO activity. Will need to generate some solubility data for DMT in DMSO.
This is from an MSDS on DMSO
"DMSO easily penetrates the skin and may enhance the rate of skin absorption of skin-permeable substances. But because of DMSO's low toxicity and its inability to carry less-permeable substances with it through the skin, it can be concluded that DMSO does not pose a significant threat by skin absorption."
Here is another source
Discover the latest and most cutting-edge news relating to drug detox & alcohol detox. Bentham is maintained by a team of expert writers covering global news in the addiction & Recovery field.
www.bentham.org
which states
"2. Lipid Disruption/Fluidisation by Chemical Penetration
Enhancers
Many enhancers, such as Azone, DMSO, alcohols, fatty
acids and terpenes, have been shown to increase permeability
by disordering or ‘fluidising’ the lipid structure of the
stratum corneum. The diffusion coefficient (D in Eq. 1) of a
drug is increased as the enhancer molecules form
microcavities within the lipid bilayers hence increasing the
free volume fraction. In some cases the enhancers penetrate
into and mix homogeneously with the lipids. However,
others such as oleic acid and terpenes, particularly at high
concentration, pool within the lipid domains to create
permeable ‘pores’ that provide less resistance for polar
molecules. These effects have been demonstrated using
differential scanning calorimetry (DSC) to measure the phase
transition temperature [131-133], electron spin resonance
(ESR) studies [134, 135], fourier transform infrared (FTIR)
[136], Raman spectroscopy [137] and x-ray diffractometry
[19]. These enhancer compounds consist of a polar head
group with a long alkyl chain [138] and are more effective
for hydrophilic permeants, although increased delivery of
lipophilic permeants has also been reported."
and this
"3. Interaction with Keratin
In addition to their effect on stratum corneum lipids,
chemicals such as DMSO, decylmethylsulphoxide, urea and
surfactants also interact with keratin in the corneocytes
[148]. It has been suggested that penetration of a surfactant
into the intracellular matrix of the stratum corneum,
followed by interaction and binding with the keratin
filaments, may result in a disruption of order within the
corneocyte. This causes an increase in diffusion coefficient,
and hence increases permeability. However in many studies
of surfactants, a close relationship between permeation
enhancement and lipid bilayer fluidisation has been observed
suggesting that the lipid lamellae of the stratum corneum
rather than the keratin of the corneocytes is the main site of
action (eg. [149]). Barry [124] suggested that these
molecules may also modify peptide/protein material in the
lipid bilayer domain to enhance permeability."
and this
"Some enhancers act inherently by multiple
mechanisms. For example, high concentrations of DMSO
(above 60%) disturb intercellular organisation, extract
stratum corneum lipids, interact with keratin and facilitate
lipid drug partitioning [3]."