I try to find efficacy of drug in septic mouse model. And I have problem with drug's solubility because it is insoluble in water (saline/PBS/etc.) So, I have to use DMSO as its solvent and I find that this DMSO based drug stock solution can be diluted up to 3 times.
And previous study, intraperitonealy injection was no use. (in diversity dose)
So I want to change route of drug administration.
(if it's no use, i try to change administration time-point)
And these are my worries.
1) There is different aspect between intravenous and intraperitoneal injection?
2) Is it possible use 25-50% DMSO based saline solution for intravenous injection?
I worry about that DMSO have a cytotoxicity effect and its effect was more severe in intravenous injection.
3) How you can deal with un-soluble materials for administration to mouse?
Any recommendations?
The injection of lipophilic substances is always a bit problematic. When we used DMSO or Oils to increase the solubility it always caused troubles (DMSO is cytotoxic and oils tend to cause sepsis (at least if injected IP)). We finally changed to 2-Hydroxypropyl-cyclodextrin (10 % in water or saline) as a solvent mediator. It always takes a while to dissolve, but it is well accepted by mice and rats even in higher volumes.
Good luck,
Volker
Hi, I am also doing therapeutics.
1)There are a significant difference as drugs enter the blood faster in intra-venous compared to intra-peritoneal. Also u need to look at which organs are u targeting. Intra-venous needs a smaller volume if compared to intra-peritoneal and the effects are faster.
2) Have a control which is injected with only DMSO to see the effects of the compound.
Try to check the stability of the compounds that u are using as different dilutes will have different effects towards the compound
Be warring. We had neurotoxcity of > 10% concentration of DMSO water solution peritoneal injection in mice in "open field" test. We observed habituation in locomotion and exploratory. It needs water control group.
http://www.research.psu.edu/arp/newsletter/spring2004.pdf
Try to dissolve the compound in oils such as peanut or olive oil
The injection of lipophilic substances is always a bit problematic. When we used DMSO or Oils to increase the solubility it always caused troubles (DMSO is cytotoxic and oils tend to cause sepsis (at least if injected IP)). We finally changed to 2-Hydroxypropyl-cyclodextrin (10 % in water or saline) as a solvent mediator. It always takes a while to dissolve, but it is well accepted by mice and rats even in higher volumes.
Good luck,
Volker
I have been working with a dmso soluble drug,administered in mice through i.p route, and as such there hasn't been any problem what so related. Because i had the same apprehension of working with dmso regarding its toxic effect and so, the best way is to check before hand the ld50 value of the solvent in the mice model you are working with. Personally i believe the solvent as a vehicle, that is required for solubility of a particular compound, should be not problematic, if so then it could be accordingly diluted at the required concentration. However there could be problem of precipitation, generally a 50:50 working solution (to the maxima) of the compound in dmso: aqueous solvent should solve the purpose. All d best.
LD50 values of DMSO in mice are about 5.8 or 9.2 g/kg as seen in the references below.
Caujolle FME, Caujolle DH. (1967). Limits of tolerance and teratogenic tolerance of dimethyl sulfoxide. Ann NY Acad Sci 141:110–25.
Willson JE, Brown DE, Timmens EK. (1965). A toxicologic study of dimethyl sulfoxide. Toxicol Appl Pharmacol 1:104–12.
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