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ABSTRACT:
Curcumin is the principle component found in turmeric. It is a well reputed anti-oxidant. It also exhibits anti-
cancerous, anti-inflammatory and anti-tumor activities. However their introduction into the clinical setting is hindered
largely due to their poor solubility and rapid metabolism, which ultimately results in poor bioavailability upon oral
administration. Therefore green nanotechnology provides a solution towards increased bioavailability of curcumin.
Drug delivery systems such as nanoparticles, micro emulsions, liposomes and blocking the degradable sites sustains
the efficacy of curcumin. This article focuses on the different forms of nanoparticle drug delivery system carried out
on curcumin and its potential uses in treating degenerative diseases.
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THERAPEUTIC USES OF CURCUMIN Table 1. Examples of some preclinical studies reported with
Curcumin shows enormous potential to combat curcumin
Animal Route Dose Findings
degenerative diseases due to its potential inhibition of
Rats Oral 1g/kg Poorly absorbed
intracellular cell signaling and induction of apoptosis. It 75% excreted in feces
intercepts various check points of metabolic pathway hence Rats Oral 2% 12nmol/L in plasma
brings about significant changes physiologically. Diet
Curcumin's diverse mechanisms of action affects cellular Mice Intraperitoneal 100 2.25 µg/ml in 15 minutes
enzymes like cyclooxygenase and Glutathione-S mg/kg Disappeared within 3 hour
Rats Intravenous 40 Disappeared within 1 hour
transferase. They exhibit immuno-modulation, cell-cell mg/kg
adhesion, gene transcription, inhibit angiogenesis and Reference taken from Shyam S. Bansal, Mehak Goel et al (2011)13
eventually induce apoptosis. Curcumin actively influences
various compounds present in the cellular apoptotic In order to overcome the problem of limiting
pathway like FLIP, Caspase 8, Caspase 10, NF-kB, p53, bioavailability, several methods of encapsulating the drug
PKC, Erk1/2, Cdc2, P13K which ultimately trigger like Liposomes, Micelles, Phospholipid Complexes and
apoptosis of the cell[5]. p53 is a tumor suppressor protein in Nanoparticles can be used. Other methods include co-
regulating the cell cycle and functions as a tumor administration of curcumin with piperine (20mg/ kg) which
suppressor in preventing cancer. Curcumin induces p53- significantly increases the curcumin bioavailability by 20-
dependent apoptosis in various cancers of colon, breast, fold in humans. Piperine causes effective inhibition of
bladder, neuron, lung, ovary, etc[6]. Curcumin particularly glucuronidation. Most of therapeutic potential of curcumin
aims at the G2/M phase of the cell cycle and arrests cell is lost due to glucuronidation that happens in liver and
division in oesophageal cancer[7]. In addition, curcumin has gastrointestinal tract. Usage of bio-conjugates like BCM-95
shown growth inhibitory effects in vitro in cancer cell lines along with turmeric oil can promote enhanced
derived from human prostate, large intestine, bone and bioavailability[14] and the use of curcumin analogues like
leukaemia[8]. Curcumin is found to inhibits skin squamous chlorogenic acid, ferulic acid, oregonin to tailor according
cell carcinoma growth and suppresses tumor progression. to specific needs[15].
Curcumin suppresses β-catenin activity, additionally,
deregulation of the Wnt/β-catenin pathway in ovarian NANOTECHNOLOGY A PROMISING POTENTIAL
cancer[9]. In a study conducted by Anupama E Gururaj et al Benefits of nanotechnology depend on the fact that it is
(2002)[10], curcumin proved to be a potent angio inhibitory possible to tailor the essential structures of materials at the
compound while tested with the help of in vivo Nano scale to achieve specific properties. Using
angiogenesis assay systems namely peritoneal angiogenesis nanotechnology, materials can effectively be made to be
and chorioallantoic membrane assay. Curcumin highlights stronger, lighter, durable, reactive, and specific. Thus the
its anti-inflammatory potential[11]. Curcumin increases the idea of incorporating curcumin and nanoparticles came into
levels of endogenous antioxidants and strengthen body's existence. Moreover, Cum-NPs showed little toxicity to
defenses against ROS. Various cell culture studies with normal tissues including bone marrow, liver and kidney at
curcumin have shown that it can inhibit secondary its therapeutic dose. Being lipophilic, curcumin
messengers and inhibit various types f cancers[12]. Despite partitions/encapsulated into the hydrophobic core of
these advantages, the compound exhibits low intrinsic amphiphilic polymers or phospholipids of NPs, which
activity, poor absorption rate, fast rate of metabolism, enhances its bioavailability and stability by automatically
inactivity of metabolic products, low retention time and separating them from the influence of degrading enzymes.
poor water solubility as shown in Table 1[13] When orally administered nanoparticles are easily absorbed
by the lympho-epithelial M cells without damage to the
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Asian J. Pharm. Tech. 2013; Vol. 3: Issue 4, Pg 218-222 [AJPTech.]
nano-particles. Shann.S.Yu et al (2012)[16], have with an encapsulation efficiency of 97.5% upon application,
demonstrated that nanoparticles can also be purposefully it is found to have increased the half-life of curcumin[12].
targeted for uptake by macrophages. The research findings
conducted by Savita Bisht et al (2011)[17] have suggested Solid lipid nanoparticles
that NanoCurc™ shows increased intrahepatic Solid lipid nanoparticles (SLN) are solid lipid particles in
bioavailability alias non-parenchymal cells (NPCs), emulsion. They can be administered parenterally, and LNs
although mechanism is unclear. In vivo pharmacokinetics can be stabilized by other surfactants or polymers and their
demonstrated that there is at least nine-fold increase in oralmixtures. A distinct advantage of SLN compared to
bioavailability of NP curcumin when compared to curcumin polymeric nanoparticle that they can be produced by high
administered with piperine as absorption enhancer [14, 15]. pressure homogenization[22]. Furthermore, they can be
stated as less toxic because of the biological origin of lipid
PREPARATION METHODS OF NANOCURCUMIN component of these SLNs while compared against
Solvent evaporation method polymeric NPs. Having such novel characteristics SLNs
As stated by S.K.Gupta et al 2004[18], the drug substance make as suitable drug delivery carriers for curcumin which
(curcumin) is either dispersed or dissolved in the owing to their lipophilic tendencies gets localized in the
polymer/solvent system and is subsequently, added to the bilayer membrane of NPs easily.
aqueous phase by continuous agitation. Agitation of the
system is continued until the solvent partitions into the NANO CURCUMIN TO TREAT DEGENERATIVE
aqueous phase and is removed by evaporation. This process DISEASES
results in hardened microsphere which contains the active Alzheimer's disease
drug. Neurodegenerative diseases involve the misfolding of
proteins which results in deposition of plaques, these
Using solvent evaporation method, Mulik et al (2009)[19] plaques are insoluble clumps of beta sheet fibrils that
coated, Poly (butyl) cyanoacrylate (PBCA) nanoparticles disrupt tissue structure and cause disease. The precursor to
with poloxamer 188 containing curcuminoids. The PBCA the plaque formation is aluminium ions, it has been shown
nanoparticles exhibited controlled drug release over a long that nano-curc binds with aluminium and inhibits the
period of time and the release was seen higher in cases of fibrillation of neurodegenerative proteins[23]. Alzheimer’s
acidic environment. disease is characterized by the presence of extracellular
deposition of aggregated amyloid-β (Aβ) peptide and
Micelle Aggregation intraneuronal accumulation of hyper phosphorylated Tau
Micelle is an aggregate of surfactant molecules dispersed in protein[24]. Curcumin promotes amyloid fibril conversion
a liquid colloid. Savita Bisht et al (2007)[17] have resulting in a reduced neurotoxicity in Drosophila[25].
formulated Curcumin-NPs that can be synthesized with the Curcumin suppressed oxidative tissue damage and reduced
help of polymerization brought about by copolymers like amyloid-β deposit in mice. Nps-Cur could be a promising
N-isopropyl acrylamide (NIPAAM),N vinyl-2- drug delivery strategy to protect neurons against oxidative
pyrrolidone(VP) and polyethylene glycol monoacrylate. damage in Alzheimer’s disease[26].
These three active compounds together spontaneously
forms micelles when synthesized in water. The hydrophobic Parkinson’s disease
NIPAAM forms the core while the other two effectively Parkinson’s disease is a disorder that affects the central
stabilize the emulsion in aqueous media[20]. The use of a co- nervous system. It is caused by the abnormal accumulation
organic solvent allows for quantitative loading of the of aggregated α-synuclein (αS) which happens due to
curcumin into the nanoparticle, minimizing drug loss during genetic mutations and exposure to neurotoxins[27] and
formulation. Additionally, this system provides a protective intracellular reactive oxygen species (ROS) that affects the
coating for the curcumin from serum proteins by mitochondria that leads to mitiochndrial disfunction. It is
enveloping it in the center of the micelle while the PEG found that curcumin can mitigate αS-induced cytotoxicity
shell provides stealth character to the formulation. These provided with the advantage that curcumin can cross the
NPs possess very low disparity with an average particle size blood barrier system in neuron degeneration [27]. In
of 50nm that enables them to freely permeate into different parkinson’s disease curcumin reduced ROS levels that has
pancreatic cancer cell lines. been generated by oligomeric α-synuclein [28,29].
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