DMSO is highly toxic by itself, it is readily absorbed by any mucosal membrane or skin, even the gloves are not resistant,posing an hazard to the operator. So the best solution could be saline or diluted ethanol, depending on curcumine solubility.Plus there is the chance that you will get unreliable results, due to the combination between the DMSO toxic effects and curcumine effect
Curcumin is a lipophillic polyphenol, hence you can't solubilise it in water. However, you can use 0.1% CMC or a similiar inert vehicle. Please note that the curcumin will form a suspension if you use 0.1% CMC. You should avoid oil based suspension or surfactancts like tween as they are reported to alter the bioavailability profile.
Yes, you may dissolve in a bit of ethanol, and then make up the volume with saline depending on the final concentration of curcumin that you are interested in. For instance whenever we use fatty acid like linoleic acid for bioassays, we dissolve in a bit of ethanol before making the volume up with water. This solves solubility problems.
Curcumine is 100% soluble in ethanol, insoluble in water or saline. I do not know the concentration that you are going to use, but you can try to dissolve, if the amount is very small in 100% ethanol, then add water or saline(I do not know either if you are going to give it by gavage or let them drink it, in this case H2O is better) until you see the start of precipitation (may be that the final concentration of EtOH will be very small, but you have to set up the appropriate controls with the same EtOH concentration). Another alternative is to dissolve curcumine in any kind of vegetable oil (may be helping with a sonicating water bath), but in this case you will have to give it to the animals by gavage, because they are not going to drink it.
IMO, use of any kind of vehicle which can alter pharmacokinetics is not recommended if you are doing comparitive BA studies. After all the vehicle is not part of your formulation/product/test. Your aim for oral delivery should not be solubility but a suitable vehicle which can deliver the test drug.
Well, Jamwal, why not mix curcumin in the food? But who is going to tell you how much food each animal has eaten and obtain reliable data? If an animal eat 10 gr and another 15 you will get stratospheric error bars. And what if they do not like the curcumin taste? Ethanol at low concentration and vegetable oil has been universally accepted as a way of administration, to be sure that every animal get the same amount. You have simply to set the appropriate controls, EtOH at low concentration or vegetable oil. We have already said the two suitable vehicles. Anything that you are going to use will alter the pharmacoavalibility. I.E.You can not take certain antibiotic with food but for others you have to do it after eating. So why make complicate a thing that already is (giving solution by gavages to mice requires a particular needle and technique, otherwise you will inject the solution in the lungs but not in the stomach killing the animal. And what about possible curcumin interaction in the stomach with the normal animal chow? Have you any idea about that? Absorption will be slower or faster?
Since curcumin is soluble in ethanol I would prepare stock solution by dissolving the curcumin in ethanol and diluting to the final stock concentration with saline or water. Subsequent dosing solutions then could be prepared by diluting further with saline or water depending on whether you are planning on administering the doses via gavage or the drinking water. If you choose to use the drinking water route be sure to measure the water volume at each change so that you can calculate the amount consumed and estimate the animals exposure.
o DMSO producer association has successfully completed the full REACH registration of DMSO (registration number 01-2119431362-50-0000). DMSO is not classified dangerous, and no exposure scenario developments are required for downstream users in Europe.
The summary of all the tox and ecotox studies performed is available on internet. feel free to contact me if you need the links.
I would add that DMSO is commercialy used as excipient in various drugs, some of them FDA approved.
" ....Other non -guideline repeated dose toxicity studies
performed by different routes of administration and with several mammalian species have also shown that DMSO produced only slight systemic toxicity. With the exception of a decrease of the body weight gain and some hematological effects (which could be secondary to an increased diuresis) at very high dose levels, the most common finding observed in these studies is changes of the refractive power of the
lens. These ocular changes were observed following repeated oral application of DMSO at doses of around 3000 mg/kg bw/d in rats for 18 months and 1000 mg/ kg bw/d in dogs for 2 years. Following repeated dermal application, the same effects were observed at doses of around 1000 mg/kg bw/d in rabbits for 30 days, in dogs for 118 days and in pigs for 18 weeks. Similar ocular changes were not observed in monkeys following dermal application at doses of up to 9000 mg/kg bw/d for 18 months (dose levels that caused marked ocular toxicity in sensitive species)"
I would avoid DMSO for oral administration. You would be better to dissolve curcumine in ethanol or some other solvent making a stock solution and then dilute to your working concentrations.
It is safe if low amount administered but because of risk of respiratary aspiration during gavage it is better used EtoH or CMC or Vegtable oil ,of course we have used DMSO as solvent for intrapertienally adminstration
Several studies demonstrated biological effects of DMSO in vitro and in vivo when it is used in higher concentration (>2 ml/kg of body in vivo) or ( >1 % in vitro). It will depend on the concentration that would will have. You can used EtOH
DMSO has a LOWER oral toxicity than ethanol in rats and mice.
http://www.sciencelab.com/msds.php?msdsId=9923955
http://www.sciencelab.com/msds.php?msdsId=9927347
Quite honestly I'm baffled that so many researchers believe DMSO is toxic. Usually, if there is observed toxicity from DMSO it means the DMSO is impure since it can carry toxic substances through biological membranes so efficiently.
I would and have used DMSO as a solvent with ethanol to dllute chemicals that are hard to get into solution but prefer to avoid it for oral administration not so much because of what is known about its toxicity but rather what is not. My preference is to get the target chemical into solution and then dilute to working cocentrations with the prefered vehicle for oral administration both to avoid toxicity as well as to allow for normal absorption from the gut.
Certainly, DMSO is an excellent vehicle; if you add a minimal amount to dissolve your compound with this solvent (70% and fresh) and then you complete the volumen with another liquid (water, saline, etanol), you enhances solubilty and absorption, too. But you must consider that this improved absorption, increases the toxicity of curcumin. So, be careful with your concentrations and doses
The problem is the solubility of the drug in DMSO ... I think you have to use a surfactant like solutol or sodium lauryl sulfate if your drug is hydrophobic !!