Curcumin

I will not delve into detail about the many aspects of curcumin , but would suggest exploration via Margaret's blog.  I restrict comment to 3 areas:

1. The apparent "harmlessness" of the compound for human consumption
2. The results of the molecular docking of curcumin with many potential molecular targets
3. The difficulties of delivering an insoluble ( in water ) molecule via the stomach , intestine and blood to the region of interest.

1 Harm

I can find no reference to any dangerous effects of taking curcumin at any dose level.

2 Docking

There is a great need to be careful about the use and over reliance upon docking studies to predict in-vivo effect.  Curcumin is thought to exist only in the enol form when dissolved in water.

enol-ket

Thus only the enol variant should be used for docking.

Many targets were selected for myeloma and curcumin was one of the many drugs selected for docking study.  One target being GADD45B is given as an example in the Myeloma page although that docking is with the Green Tea phenol EGCG

The docking studies are well and good but the real problem then arises that if one decides it would be good to get a curcumin molecule into the bone marrow then how on earth do you do it.  It is a long fraught path from mouth to bone marrow. Stomach acid and intestine alkalinity along with water are potential degradation chemicals. Intestinal absorption is a whole topic and blood transfer complex.

However a starting position for any drug application must be than the intestinal absortion size must be below 100nm and blood transport via albumin must be single molecules in solution.  This gives curcumin an immediate problem because the blood levels for oral consumption of very high doses as shown below are below 4uM and most of the time around 1uM.


cc-blood

This must be considered in the light of the effective doses as illustrated below.

cc-ld50
The LD50 concentration varies from 13 to 56 uM (being achieved by dissolving into DMSO).

Hence it would appear that oral consumption might just allieviate some myrloma ( at 30% of LD50 ) but in the worst case disease providing only 7% of LD50 is unlikely to do the job.  We have to assume that solubility is one major key to delivering the drug to the target. 



3 Solubility

3a Powder

Curcumin solubility in water is approximately 3mg per litre.  Even with maximum intestinal absorption the 5 litres of blood we have could only hold 15mg dissolved.

3b Solid dispersions  SD

By enclosing single molecules of curcumin ( very hydrophobic) in molecules such as vinylpyrollidone ( very hydrophillic ) we appear to be able to deliver amorphous curcumin into solution. My most rapid and concentrated solutions resulted from ( by mass) 1 part of curcumin and 7 parts of vinylpyrollidone.
For further details search and refer to  "Comparative study of curcumin and curcumin formulated in a solid dispersion - Evaluation of their antigenotoxic effects"

3b Self nano emulsifying  SNEDDS

3c Chemical shielding  CS

Here we are talking about major changes to the delivery of curcumin.  I refer you to Brad Culkin's site.  I find the technique unexplainable , unlikely and of profound effect.  The site may be a little out-of-date in the detail but the basics seem to provide for a concentrated and protected delivery of curcumin to the blood.







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