Curcuminoid

A curcuminoid is a linear diarylheptanoid, with molecules such

as curcumin or derivatives of curcumin with different chemical groups that have been
formed to increase solubility of curcumins and make them suitable for drug formulation.
These compounds are natural phenols and produce a pronounced yellow color.
Many curcumin characters are unsuitable for use as drugs by themselves. They have
poor solubility in water at acidic and physiological pH, and also hydrolyze rapidly
in alkaline solutions. Therefore, curcumin derivatives are synthesized to increase their
solubility and hence bioavailability.[1] Curcuminoids are soluble in dimethyl
sulfoxide (DMSO), acetone and ethanol,[2] but are poorly soluble in lipids. It is possible to
increase curcuminoid solubility in aqueous phase with surfactants or co-surfactants.
[3]
 Curcumin derivatives have been synthesized that could possibly be more potent than
curcumin itself. Most common derivatives have different substituents on the phenyl
groups.[2] There is an increasing demand of late for demethoxycurcumin and other
curcuminoids because of their recently discovered biological activity.[3]

Cyclodextrins[edit]
Curcuminoids form a more stable complex with solutions which
contain cyclodextrin towards hydrolytic degradations.[4] The stability differs between size
and characterization of the cyclodextrins that are used.[1] Dissolution of
demethoxycurcumin, bisdemethoxycurcumin and curcumin are greatest in the
hydroxypropyl-γ-cyclodextrin (HPγCD) cavity. The curcuminoids which have
a substituent connected to the phenyl groups show more affinity for the HPγCD
compound. Degradation rate is depended on pH of the solution and how much
protection the cyclodextrins provide the curcuminoids. The derivatives are usually more
stable than curcumin against hydrolysis in cyclodextrin solution. No covalent bonds are
present between the cyclodextrins and the curcuminoids so they are easily released
from the complex by simple solvent effects.[2]

Micelles and nanoparticles[edit]

A drug design with curcuminoids in complex with micelles could be one solution of the
insolubility of the curcuminoids. The curcuminoids would be in complex with the core of
the micelles similar to the complex inside the cyclodextrins. The micelles are dissolved
in a suitable solvent where the headgroups of the micelles interact with the solvent.
Curcuminoids as loaded solid lipid nanoparticles (SLN) have been developed with great
success by using microemulsion technique. The loading capacity, the mean particle size
and size distribution are all factors that have to be considered when the effects of
curcuminoids in different strength are observed because it could variate.[2] The
advantages of SLN are the possibilities of controlled drug release and drug targeting,
protection of incorporated compound against chemical degradation, no biotoxicity of
the carrier, avoidance of organic solvent and no problems with respect to large scale
production.[2] In vitro studies show a prolonged release of curcuminoids from the
nanoparticle preparate up to 12 hours and the curcuminoids maintained their physical
and chemical stability after 6 months of storage in the absence of light at room
temperature. The sensitivity of curcuminoids to light and oxygen is greatly reduced
by formulation of curcuminoids in SLN.[2]
Solid lipid nanoparticles for cosmetics[edit]
Solid lipid nanoparticles preparate has been developed for cosmetics where the
curcuminoids are used in cream base. But there are some stability issues which have
not been overcome yet, further studies need to be done to find a suitable formulation
which can be carried out in order to prolong the stability of the curcuminoids.
Nevertheless, there have been improvements in formulation of some stable model
cream preparations with SLN curcuminoids.[2] It is suggested that most of the
curcuminoids are incorporated at the SLN surface where they are diffused into the
cream matrix until a steady state is reached. At this state the curcuminoids go from the
cream to the dissolution medium. A possible burst release in creams containing
curcuminoids have been reported where the curcuminoids are rapidly released in a
sufficient amount from the cream into the skin and is followed by a controlled release.
[2]
 When SLN are prepared by microemulsion at a temperature with the range of 70–
75 °C an oil-in-water microemulsion is spontaneously formed. The SLN are obtained
immediately when they are dispersed in the warm microemulsion into cold water, with
the help of a homogenizer. The cold water facilitates a rapid crystallization of the lipids
and therefore prevents aggregation of the lipids. After freeze drying the yellow
curcuminoids containing SLN were obtained and could easily be redispersed in water
and the model cream. The SLN have uniform distribution and according to electron
micrograph scan they had a spherical shape and smooth surface.[2] It has been reported
that increasing the lipid content over 5–10%(w/w) increased the mean particle size and
broader size distribution in most common cases. That range should there for be
ideal concentration for formulation of the SLN.[2]
Incorporation and formulation[edit]
Incorporation is one thing that needs to be considered in formulation of SLN.
Concentration of the lipid, emulsifier and co-emulsifier solution is a key factor on
this conversion of the SLN. If the amount of emulsifier and co-emulsifier are increased
but the lipid amount is constant the surface of the SLN which is formed will be too small
to adsorb all the surfactant and co-surfactant molecules, and a formation of
curcuminoids solution micelles will be created. This will then increase the water
solubility of the curcuminoids and they could partition from the SLN into the micelles that
were formed during a wash procedure. This will reduce the final incorporation efficacy
on the surface of the SLN.[2]

Anti-oxidant activity[edit]
The curcumin derivatives demethoxycurcumin and bisdemethoxycurcumin have, like
curcumin itself, been tested for their antioxidant activities in vitro.[3] Antioxidants can be
used to extend the shelf life for food and maintain their
safety, nutritional quality, functionality and palatability.[3] Pure chemicals of curcumin and
its derivatives are not available in the open market. Commercially available curcumin
contains 77% curcumin, 17% demethoxycurcumin and 3% bisdemethoxycurcumin from
the herb Curcuma longa. Curcumin is mainly produced in industry as pigment by
using turmeric oleoresin as the starting material which curcuminoids can be isolated
from. After the isolation of the curcuminoids, the extract which is about
75% liquor mainly contains oil, resin and more curcuminoids which can be isolated
further. This isolation method was used to demonstrate the antioxidant activities of
curcuminoids, where they isolated pure curcuminoids from the main liquor.
[3]
 One research reported that curcumin was the strongest antioxidant,
demethoxycurcumin the second strongest and bisdemethoxycurcumin the
least effective. Curcuminoids nevertheless showed activity against oxidation.
Curcuminoids act as a superoxide radical scavenger as well
as singlet oxygen quencher and gives the antioxidant its effectiveness.
[3]
 Tetrahydrocurcumin, one of the main metabolites of curcumin, is the most potent
antioxidant among the naturally occurring curcuminoids.[3] The curcuminoids are capable
of inhibiting damage to super coiled plasmid DNA by hydroxyl radicals. It was concluded
that the derivatives of curcumin are good in trapping the 2,2-diphenyl-1-
picrylhydrazyl (DPPH) radical as efficiently as curcumin which is a well known
antioxidant.[3]