Synthesis of Curcumin Nanoparticles From Raw Turmeric Rhizome

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Synthesis of Curcumin Nanoparticles from Raw Turmeric Rhizome


Sandhuli S. Hettiarachchi, Shashiprabha P. Dunuweera, Asiri N. Dunuweera,
and R. M. Gamini Rajapakse*
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ABSTRACT: Turmeric (Curcuma longa L.) has been used as a


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spice and a medicinal herb since ancient times. The main active
ingredient of turmeric is curcumin, a polyphenol that helps prevent
and control neurological, respiratory, cardiovascular, metabolic,
inflammatory, and autoimmune diseases and some cancers.
Downloaded via 49.36.110.124 on May 13, 2021 at 22:44:24 (UTC).

However, curcumin has drawbacks such as low water-solubility,


poor absorption, fast metabolism, quick systemic elimination, low
bioavailability, poor pharmacokinetics, low stability, and low
penetration targeting efficacy. To overcome these drawbacks, a
common method used is encapsulating curcumin in nanocarriers
for targeted delivery. However, the degraded products of
nanocarriers have raised concerns. In this research, we synthesized
nanoparticles of curcumin, nanocurcumin without using nano-
carriers. To do so, curcumin was soxhlet extracted from raw turmeric rhizome. The stock solutions of different curcumin
concentrations prepared in dichloromethane were added to boiling water at different flow rates and sonicated for different time
intervals. An average particle size of 82 ± 04 nm was obtained with 5.00 mg/mL stock solution concentration, at 0.10 mL/min flow
rate and 30 min sonication time. The particle size tends to increase with the flow rate and the concentration of curcumin in the stock
solution but decreases with the sonication time. X-ray diffraction shows sharp and intense diffraction peaks for curcumin, indicating
its identity and high crystallinity, but nanocurcumins are amorphous. Fourier-transform infrared spectroscopy spectra confirm the
presence of all the functional groups of curcumin in nanocurcumin. Transmission electron microscopy and scanning electron
microscopy images show the perfectly spherical morphology of nanocurcumin. Although curcumin is not water-soluble, nano-
curcumin formulations are freely dispersible in water.

■ INTRODUCTION
Nanotechnology is a field of modern applied science that aims
side), camptothecin and its derivatives (topotecan and
irinotecan), anthracyclines (doxorubicin, daunorubicin, epi-
rubicin, and idarubicin), and many others.7 Their targeting
to develop materials and devices with unique and inherent
toward diseased cells, tissues, and organs is currently under
properties, in their size of 1−100 nm, at least in one
intense investigation. This has been achieved by developing
dimension.1 Nanomedicine is a branch dealing with the
nanodosage formulations in carriers such as polymeric
applications of nanotechnology in the treatment, diagnosis,
nanoparticles (nanospheres and nanocapsules), liposomes,
monitoring, and control of biological systems.2 The use of
proliposomes, solid lipid nanoparticles, nanoemulsions, in-
nanomaterials in targeted drug delivery (TDD) systems is
organic nanoparticles, and biological nanomaterials such as red
gaining increased attention in cancer chemotherapy,3 over-
blood cells, DNA, and so forth as drug and vaccine
coming microbial resistance to antibiotics,4 and in the safe and
carriers.8−14 The encapsulation of the active ingredients
efficient delivery of vaccines, including newly developed SARS-
isolated from plant products, such as curcumin from turmeric,
CoV-2 vaccines.5 The use of nanoparticle carriers in TDD
in such nanocarriers for TDD, has been recently reported.15−17
systems is found to result in enhanced solubility, stability, While encapsulated drugs in nanocarriers have many benefits,
bioavailability, and pharmacological activity while avoiding the toxicity issues of the degraded products of nanocarriers,
physical and chemical degradation, cytotoxicities to healthy
cells, and higher dosage requirements.6 Among these, the drugs
and formulations derived from natural sources, such as plants Received: December 28, 2020
and minerals, are gaining upsurged worldwide attention. In Accepted: March 8, 2021
fact, half of the approved anticancer drugs have plant-based Published: March 18, 2021
origin, which include vinca alkaloids (vincristine, vinblastine,
vindesine, and vinorelbine), taxanes (paclitaxel and docetaxel),
podophyllotoxin and its derivatives (etoposide and tenipo-
© 2021 The Authors. Published by
American Chemical Society https://doi.org/10.1021/acsomega.0c06314
8246 ACS Omega 2021, 6, 8246−8252
ACS Omega http://pubs.acs.org/journal/acsodf Article

such as liposomes, have become a concern. Such concerns can been used as the extraction solvent due to its high
be avoided if the nanoparticles could be made directly from the solubilization capacity.28 As such, in this study, we used the
drug molecules without having to use separate nanocarriers. soxhlet extraction to isolate curcumin and purposely developed
With this idea in mind, we investigated the synthesis of a mechano-chemical method to synthesize nanocurcumin.
nanoparticles of curcumin, which we call nanocurcumin, from
curcumin extracted from turmeric by developing a novel and
inventive methodology based on mechano-chemical synthesis.
■ RESULTS AND DISCUSSION
The moisture percentage, volatile oil percentage, oleoresin
The reason for choosing curcumin is because it has been percentage, and the curcumin percentage of the obtained
used as a traditional medicine for the diseases such as biliary turmeric powder are 10.00 ± 0.01, 5.85 ± 0.05, 17.55 ± 0.05,
disorders, anorexia, cough, diabetic wounds, hepatic disorders, and 6.47 ± 0.01, respectively (see Supporting Information:
rheumatism, and sinusitis.18,19 Recent studies have revealed Figure S1). Accordingly, the quality parameters of the turmeric
that turmeric has anticancer activity as well.20−22 However, the powder complied with the standards; thus, it can be confirmed
yield and the quality of curcumin obtained depend on the that good quality turmeric powder was obtained. Curcumin
methods of turmeric processing and curcumin extraction. was successfully extracted from turmeric powder. 2.60 ± 02 g
Different methodologies are used to process turmeric though it of crude extract was obtained from 15.00 g of ground turmeric
consists mainly of four basic steps: washing, curing, drying, and powder. 0.40 ± 0.02 g of crude curcuminoid powder was
polishing.23 Color, aroma, and other chemical properties of extracted from 1.00 g of the crude extract. 0.30 ± 0.01 g of
processed turmeric directly depend on the processing crystalline curcumin was obtained from 1.00 g of crude
procedure.24 Therefore, specific optimum parameters should curcuminoid powder. Accordingly, the percentage extract-
be used to process the turmeric rhizomes to obtain a maximum ability of crude extract, crude curcuminoid powder, and
yield of volatile oil and oleoresin, safeguarding the chemical crystalline curcumin, with respect to the turmeric powder, is
constituents in turmeric. There are specifications given by 17.49 ± 0.14, 6.95 ± 0.31, and 5.16 ± 0.44%, respectively (see
organizations such as the American Spice Trade Association Supporting Information: Figure S2). The particle size of the
(ASTA), the Food and Drug Administration (FDA), and the synthesized nanocurcumin was studied using dynamic light
Sustainable Livelihood Security Index (SLSI) regarding the scattering (DLS), and the distributions of the hydrodynamic
maximum and minimum levels of particular compounds in diameter of the synthesized particles are shown in Figure 2.
turmeric powder.23 Turmeric powder contains about 60−70%
carbohydrates, 6−13% water, 6−8% protein, 5−10% fat, 3−7%
dietary minerals, 3−7% volatile oil, 2−7% dietary fiber, and 1−
9% curcuminoids.23 About 235 compounds have been
identified in turmeric, they are categorized under phenolic
compounds and terpenoids.25 The identified compounds
consist of 22 diarylheptanoids, 8 phenylpropene, other
phenolic compounds, 68 monoterpenes, 109 sesquiterpenes,
5 diterpenes, 3 triterpenoids, 4 sterols, 2 alkaloids, and 14
other compounds.25 Curcuminoids are comprised of curcumin,
demethoxycurcumin, and bisdemethoxycurcumin, which all
belong to the diferuloylmethane group of phenolic com-
pounds.26,27 The percentage composition of curcuminoids
depends on geographical conditions; it roughly contains 80%
curcumin, 17% demethoxycurcumin, and 3% bisdemethox-
ycurcumin.28 The most important active ingredient is
curcumin, and its chemical structure is shown in Figure 1.

Figure 1. Chemical structure of curcumin.29

Widely used methods to extract curcumin from the turmeric


rhizome are soxhlet extraction, microwave-assisted extraction,
supercritical fluid extraction, enzyme-assisted extraction, and Figure 2. Particle size distribution of synthesized nanocurcumin.
ultrasound-assisted extraction.28,30 Soxhlet extraction is one of
the foremost and most common extraction techniques that
allow the sample to repeatedly contact with the solvent, thus Since there is a single peak in the distribution of the
enhancing the extraction yield of the target compound.28 hydrodynamic diameter, it can be assumed that spherical
Further, since curcumin is a liposoluble compound, organic particles have been synthesized. The average hydrodynamic
solvents such as hexane, acetone, methanol, isopropanol, ethyl diameter of each treatment was statistically analyzed. The
acetate, and ethanol have been used for extractions in results are depicted in Table S2. Mean values were
turmeric.31,32 In most extraction experiments, ethanol has comparatively analyzed according to the analysis of variance
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(ANOVA) procedure. Since the P-value is lower than the alpha vibrations of the functional groups present in curcumin and
P value (P = 0.0001, therefore P < 0.05), the null hypothesis is nanocurcumin, as detailed below (Table 1).
rejected. There was a significant difference between the average
hydrodynamic diameters of the synthesized nanocurcumin
particles at a 0.05 significance level. Duncan comparison
analysis was carried out between the treatments to find out
which means are different. There are significant differences
between some treatments, while some treatments did not have
significant differences. The smallest average hydrodynamic
diameter is 82 ± 04 nm, which is from treatment 01. The
highest average hydrodynamic diameter is 316 ± 15 nm, which
is from treatment 12 (see Figure 2).
According to the results, the particle size is proportional to
the flow rate and the curcumin concentration of the stock
solution, while it is inversely proportional to the sonication
time.33 The absorption spectrum of curcumin results in an
absorbance peak at 415 nm, and the absorption spectrum of
nanocurcumin results in an absorbance peak of 411 nm (see
Supporting Information: Figure S3). Since the characteristic
feature of curcumin and nanocurcumin is obtained, it can be
confirmed that curcumin and nanocurcumin are synthesized
successfully.34,35
The crystallinity and purity nature of curcumin and
nanocurcumin were analyzed using XRD, a strong analytical
tool used to assess the purity nature and crystalline phases of
sample particles (Figure 3). Accordingly, it shows that the

Figure 4. FTIR spectra of curcumin and nanocurcumin.

Table 1. Functional Groups Responsible for IR Absorption


of Curcumin and Nanocurcumin
wavenumbers (1/λ) (cm−1)
functional groups, along with the mode of
curcumin nano-curcumin vibration
3501 3350 stretching vibration of hydrogen-bonded O−H
2916 2922 asymmetric stretching vibrations of Csp2−H
2847 2850 asymmetric stretching vibrations of Csp3−H
1625 1623 C−H bending frequency of the aromatic
overtone
1600 1581 stretching vibration of double-bonded CC
1501 1503 stretching vibration of conjugated carbonyl
(CO) group
1454, 1447, 1424 aromatic stretching vibrations of the benzene
1423 ring
1266 1262 stretching vibration of Csp2−O bond
1154 1118 stretching vibration of Csp3−O bond

The intense band at wavenumber 3501 cm−1 corresponds to


the stretching vibration of hydrogen-bonded O−H present in
curcumin. Bands at 2916 and 2847 cm−1 originate from
Figure 3. XRD pattern of curcumin and nanocurcumin.
asymmetric stretching vibrations of Csp2−H and Csp3−H bonds,
respectively. C−H frequency of the aromatic overtone is
synthesized curcumin is pure and crystalline, whereas the obtained at 1625 cm−1. Bands at 1454 and 1423 cm−1
synthesized nanocurcumin is amorphous.34 Curcumin demon- correspond to the aromatic stretching vibrations of the
strated sharp, intense diffraction peaks at 2θ values of 9.04, benzene ring. The intense characteristic band centered at
12.35, 14.68, 17.42, 18.30, 23.46, 24.75, 25.75, and 27.53°, 1501 cm−1 corresponds to the stretching vibration of the
indicating its purity and high crystalline nature. conjugated carbonyl (CO). The band centered at 1600
The Fourier transform infrared spectroscopy (FTIR) spectra cm−1 originates from double-bonded carbon stretching
of curcumin and nanocurcumin were scanned at the mid- vibration, while bands centered at 1266 cm−1 and centered
infrared region (4000−400 cm−1), and the spectra are depicted at 1154 cm−1 originate from the stretching vibrations of Csp2−
in Figure 4. The bands obtained correspond to the respective O and Csp3−O bonds, respectively.32,36
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Considering nanocurcumin, the broad, intense band at


wavenumber 3350 cm−1 corresponds to the stretching
vibration of hydrogen-bonded O−H present in nanocurcumin.
Asymmetric stretching vibrations of Csp2−H and Csp3−H are
shown at 2923 and 2850 cm−1, respectively. C−H frequency of
the aromatic overtone is obtained at 1623 cm−1. Bands at 1447
and 1424 cm−1 correspond to the aromatic stretching
vibrations of the benzene ring. The intense characteristic
band centered at 1503 cm−1 corresponds to the stretching
vibration of the conjugated carbonyl (CO). Stretching
vibrations of double-bonded carbon, Csp2−O, and Csp3−O
bonds are shown at 1581, 1262, and 1118 cm−1, respectively.
The shape, size, morphology, and surface texture of the
curcumin nanoparticles could be detected using numerous
sophisticated analytical techniques such as transmission
electron microscopy (TEM) or scanning electron microscopy
(SEM).
Based on the TEM image shown in Figure 4a, the
nanocurcumin shows perfectly spherical polydisperse particles
with an average diameter of around 100−200 nm. Most of the
visible nanoparticles showed a round and smooth surface in
TEM. The SEM of nanoparticles further proved their smooth
surface texture (Figure 4c,d). On the other hand, higher
sonication leads to higher fluidization by which nanocurcumin
is distributed more uniformly to produce a homogeneous
dispersion and triggers more efficient loading. Besides, frequent Figure 5. TEM images of the spherical nanocurcumin synthesized
collisions among curcumin nanoparticles lead to less from treatment 01 are detailed in Table S1 (a) 100k magnification
and (b) 200k magnification. SEM images of spherical nanocurcumin
accumulation. When curcumin and nanocurcumin were (c) 500 nm resolution (d)100 nm resolution.
dispersed in water to study and compare the behavior of
particles in water, curcumin is not soluble in water, while
nanocurcumin is freely dispersible in water (see Supporting
Information: Figure S4).37 appears as clumps in water, it does not tend to become
nanocurcumin under normal sonication conditions.


The extracted curcumin is highly crystalline. During the
formation of nanocurcumin, there was a sudden temperature
change when adding into hot water, which was under CONCLUSIONS
sonication condition. This may have changed the crystalline Raw turmeric rhizomes are processed to obtain turmeric
nature of curcumin resulting in an amorphous nature in the powder with 6.47 ± 0.01% curcumin percentage. Curcumin is
synthesized nanocurcumin.38,39 Dichloromethane is a solvent successfully extracted from turmeric powder using the soxhlet
that dissolves curcumin.40 However, once we dissolve them in extraction method, and the extractability of curcumin is 5.16 ±
dichloromethane, curcumin molecules get separated. When 0.44%. The mechano-chemical fabrication method is used to
boiling water is added, the solvent dichloromethane evaporates synthesize nanocurcumin from the extracted curcumin. When
since its boiling point is below the boiling water temperature. curcumin and nanocurcumin are dispersed in water, curcumin
This evaporation of solvent helps the curcumin molecules to is not soluble in water, while nanocurcumin is freely dispersed.
self-assemble in all directions. Since molecules are assembling However, there is no change between the chemical structures
from all directions, the resultant nanoparticles assume a of curcumin and nanocurcumin. According to the results, the
perfectly spherical morphology, as witnessed by their TEM particle size of nanocurcumin increases with the flow rate and
images (see Figure 5a,b). the curcumin concentration of the stock solution, while it
Nanoparticle formation depends on two factors: nucleation decreases with the sonication time. TEM and SEM images
and growth.41 The relative kinetics of these two processes provide evidence of spherical and smooth surface morphology
determines the size and shape of the nanoparticles formed.42 and the size range between 100 and 200 nm. In contrast, the
Since nucleation happens throughout the solution and each other analytical techniques such as UV−visible spectroscopy,
nucleus formed undergo subsequent growth, depending on the FTIR, and XRD further confirm the characteristic features of
concentration of the initial molecules and rates of these two nanocurcumin synthesis. The present study is the first evidence
processes, the particle formed assumes the said size and the to synthesize nanocurcumin, using the natural turmeric
shape.43,44 The flow rate should be very low to form rhizome as the raw material, bringing a new insight on natural
nanocurcumin in the nanorange. Using a higher flow rate or substances such as turmeric.
turbulent addition leads to particle aggregation, thus leading to
the increase of particle size. When we add a drop of curcumin
dissolved in dichloromethane, at a very low flow rate, the
■ MATERIALS AND METHOD
Materials. Toluene, ethanol, hexane, isopropyl alcohol, and
solvent evaporates suddenly, and the available curcumin dichloromethane of analytical grade were purchased from
remains in the water. Still, it does not tend to agglomerate Sigma-Aldrich. The raw turmeric rhizomes were obtained from
due to the sonication condition, which results in nano- the locally grown turmeric plants in the Ampara district in the
curcumin. Although curcumin does not dissolve in water and Eastern Province of Sri Lanka.
8249 https://doi.org/10.1021/acsomega.0c06314
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Methods. Turmeric rhizomes were cleaned well; the fingers tometer from wavenumbers 4000−400 cm−1 to identify the
and the mother rhizomes were separated and blanched in a chemical composition and bonding present.
closed pot filled with 3/4 of water for 30 min and 45 min, The mean particle diameter of nanocurcumin was
respectively. The rhizomes were dried under sunlight until the investigated using DLS, CILAS particle size analyzer
moisture percentage was reduced to 10%. Then, the removal of NANO DS. 5.00 mg of nanocurcumin was dispersed in 30.0
the skin in the rhizomes was done by the turmeric polisher mL of distilled water and sonicated for 15 min. The colloidal
machine, and it was ground using the grinder (I.K.A. solution was then diluted with distilled water in a 1:1 ratio and
Laboratechnik 6000 min−1, France) to obtain turmeric powder. sonicated again, and the colloidal solution was used for size
The moisture percentage of the turmeric powder was distribution analysis. Each experiment was performed in
determined by the Dean and Stark method (AOAC 17th triplicates. Data were analyzed using ANOVA using the SAS
edition 2000 Official Method 986.21) which was used to 9.0 statistical package at 5% level of significance. Means were
determine the volatile oil percentage of turmeric powder. The compared with Duncan’s Multiple Range Test. The morpho-
soxhlet extraction method was used to determine the oleoresin logical analysis of nanocurcumin was conducted by TEM
percentage using ethanol as the solvent. ASTA 18.0 method (JEOL JEM-3010) operating at 300 kV. SEM images were
was used to determine the curcumin content of the turmeric obtained using a FEI Quanta 450 FEG-SEM microscope
powder.45 operating at 30 kV. 5.00 mg of nanocurcumin was dispersed in
Curcumin was extracted using the soxhlet extraction 30.0 mL of ethanol. The particle dispersion prepared was
method. To do so, ground turmeric powder was weighed. A evaporated to dryness and was analyzed by coating on the
sample of 15.00 g was embedded in a thimble and put in the surface of carbon and sputtering with gold.
soxhlet apparatus, which was gradually filled with ethanol as
the extraction solvent. The extraction was carried out at 60 °C
for 8 h by then; all the colored compounds are extracted to the

*
ASSOCIATED CONTENT
sı Supporting Information
solvent. Upon completing the extraction, the ethanol was The Supporting Information is available free of charge at
separated from the extract using the rotary evaporator https://pubs.acs.org/doi/10.1021/acsomega.0c06314.
(Heidolph, Germany). 1.00 g of the crude extract was mixed
with 25.0 mL of hexane, stirred gently, and was kept for 12 h. Quality parameters of turmeric powder ; extractability of
The solution was then stirred using the magnetic stirrer (Velp crude extract, crude curcuminoid powder, and crystalline
Scientifica, Europe) at 600 rpm for 3 h to obtain the powder. curcumin with respect to turmeric powder; UV−visible
The solution was centrifuged. The powder obtained was spectra of curcumin and nanocurcumin; aqueous
separated and dried at 40 °C in the oven for 2 h. 1.00 g of the dispersion of particles (a) curcumin in water and (b)
crude curcuminoid powder was mixed with 10.0 mL of a hot colloidal dispersion of nanocurcumin in water; different
solvent mixture of isopropyl alcohol: hexane in 1:1.5 molar treatments used in the experiment to synthesize
ratio.32 The solution was then cooled at room temperature to nanocurcumin; and average particle size of synthesized
obtain pure crystalline curcumin, and the extracted curcumin nanocurcumin (particle sizes with the same letter are not
was separated by filtration. significantly different; p value < 0.05 was considered as
Nanocurcumin was synthesized by a physicochemical statistically significant difference; one-way ANOVA was
fabrication method. The stock of curcumin solution (5.00 applied) (PDF)


mg/mL) was prepared by dissolving the extracted curcumin
powder in 20.0 mL of dichloromethane. 1.00 mL of stock AUTHOR INFORMATION
solution was added to 50.0 mL of boiling water, in a dropwise
manner at 0.1 mL/min flow rate, under ultrasonication Corresponding Author
conditions (Velp Scientifica, Europe). The solution was R. M. Gamini Rajapakse − Department of Chemistry, Faculty
sonicated for 30 min. Then, the mixture was stirred at 800 of Science, University of Peradeniya, Peradeniya 20400, Sri
rpm for 20 min till an orange-colored precipitate was obtained. Lanka; orcid.org/0000-0003-3943-5362; Email: rmgr@
The supernatant was discarded, and the synthesized nano- pdn.ac.lk
curcumin was obtained for further studies. The effect of the
Authors
curcumin concentration of the stock solution, flow rate, and
the sonication time was examined to achieve an optimal Sandhuli S. Hettiarachchi − Department of Chemistry,
formulation of nanocurcumin. Accordingly, twelve treatments Faculty of Science, University of Peradeniya, Peradeniya
were used to synthesize nanocurcumin by changing the 20400, Sri Lanka; orcid.org/0000-0001-7122-8772
concentration of the stock solution, flow rate, and the Shashiprabha P. Dunuweera − Department of Chemistry,
sonication time, as shown in Table S1. Faculty of Science, University of Peradeniya, Peradeniya
The absorbance spectra were scanned using UV−visible 20400, Sri Lanka; orcid.org/0000-0003-0197-423X
spectrophotometry (Agilent Cary 60, Australia) in the range of Asiri N. Dunuweera − Department of Basic Science, Faculty of
200−800 nm wavelengths. The diffraction pattern was Allied Health Sciences, University of Peradeniya, Peradeniya
recorded by a Bruker D8 ADVANCE Eco powder X-ray 20400, Sri Lanka; orcid.org/0000-0002-6564-7337
diffractometer (XRD) with Cu Kα radiation of wavelength λ = Complete contact information is available at:
0.154 nm, incident at an angle of 1° and 2θ intervals from 20° https://pubs.acs.org/10.1021/acsomega.0c06314
up to 80° with the step size 0.005°. The dried powder sample
was placed on a Smart iTR attenuated total reflectance (ATR) Author Contributions
accessory composed of diamond crystal as the sample holding The manuscript was written through the contributions of all
technique at a controlled ambient temperature (25 °C). The authors. All authors have given approval to the final version of
sample was scanned using a Jasco FTIR 6700 spectropho- the manuscript.
8250 https://doi.org/10.1021/acsomega.0c06314
ACS Omega 2021, 6, 8246−8252
ACS Omega http://pubs.acs.org/journal/acsodf Article

Notes Coated Antibacterial Activated Carbon for Water Purification. RSC


The authors declare no competing financial interest. Adv. 2015, 5, 64696−64703.


(16) Madusanka, N.; De Silva, K. M. N.; Amaratunga, G. A
ACKNOWLEDGMENTS Curcumin Activated Carboxymethyl Cellulose-Montmorillonite Clay
Nanocomposite Having Enhanced Curcumin Release in Aqueous
This research is fully supported and funded by the University Media. Carbohydr. Polym. 2015, 134, 695−699.
of Peradeniya and the Postgraduate Institute of Science (17) Jayaweera, H. D. A. C.; Siriwardane, I.; Silva, K. M. N. D.; Silva,
(PGIS) university of Peradeniya, Sri Lanka. We thank all our R. M. D. Synthesis of Multifunctional Activated Carbon Nano-
colleagues who provided insights and expertise that greatly composite Comprising Biocompatible Flake Nano Hydroxyapatite
assisted the research in various ways. and Natural Turmeric Extract for the Removal of Bacteria and Lead

■ ABBREVIATIONS
DLS, dynamic laser light scattering; XRD, X-ray diffractom-
Ions from Aqueous Solution. Chem. Cent. J. 2018, 12, 1−14.
(18) Asghari, G.; Mostajeran, A.; Shebli, M. Curcuminoid and
Essential Oil Components of Turmeric at Different Stages of Growth
Cultivated in Iran. Res. Pharm. Sci. 2009, 4, 55−61.
etry; FTIR, Fourier transform infrared spectroscopy; TEM,
(19) Naganuma, M.; Saruwatari, A.; Okamura, S.; Tamura, H.
transmission electron microscopy; SEM, scanning electron Turmeric and Curcumin Modulate the Conjugation of 1-Naphthol in
microscopy; ATR, attenuated total reflectance; ANOVA, Caco-2 Cells. Biol. Pharm. Bull. 2006, 29, 1476−1479.
analysis of variances


(20) Kuttan, R.; Bhanumathy, P.; Nirmala, K.; George, M. C.
Potential Anticancer Activity of Turmeric (Curcuma Longa). Canc.
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