Sains Malaysiana 47(5)(2018): 977–989
http://dx.doi.org/10.17576/jsm-2018-4705-13
Inclusion of Curcumin
in β-cyclodextrins as Potential Drug Delivery
System: Preparation, Characterization and Its Preliminary Cytotoxicity
Approaches
(Penambahan
Kurkumin dalam β-siklodekstrin
sebagai Potensi
Sistem Penyampaian Ubat: Penyediaan, Pencirian dan Pendekatan
Awal Kesitotoksikan)
MUHAMMAD
HASNOR
JA'FAR1,
NIK
NUR
SYAZNI
NIK
MOHAMED
KAMAL1,
BOON
YIH
HUI1,
MUHAMMAD
FAHMI
KAMARUZZAMAN1,
NUR
NADHIRAH
MOHAMAD
ZAIN1,
NOORFATIMAH YAHAYA1 &
MUGGUNDHA
RAOOV*2,3
1Integrative
Medicine Cluster, Advanced Medical & Dental Institute, Universiti
Sains Malaysia, 13200 Pulau
Pinang, Malaysia
2Department
of Chemistry, Faculty
of Science, University
of Malaya, 50603
Kuala Lumpur, Federal Territory, Malaysia
3Universiti Malaya Centre for Ionic Liquids
(UMCiL), Department
of Chemistry, Faculty
of Science, University
of Malaya, 50603
Kuala Lumpur, Federal Territory, Malaysia
Diserahkan: 2
September 2017/Diterima: 5 Disember 2017
ABSTRACT
The development and application
of organic based drug carrier in drug delivery system (DDSs)
with greater efficacy and fewer side effects remains a significant challenge in
modern scientific and medical research. The aim of current study was to
evaluate the ability of β-cyclodextrin (β-CD)
as drug delivery carrier to encapsulate Curcumin (CUR),
a promising chemotherapeutic that exhibits low aqueous solubility and poor
bioavailability forming inclusion complex by kneading method to enhance its
delivery to cancer cells. Different methods and analysis such as Fourier
Transform Infrared (FTIR) spectrometer, 1H
Nuclear Magnetic Resonance (1H NMR),
X-Ray Diffraction (XRD), Scanning Electron Microscope (SEM)
and Thermo-gravimetric Analysis (TGA) were employed to approve
the successful formation of the inclusion complex where the aromatic ring of CUR has
been encapsulated by the hydrophobic cavity of β-CD. UV absorption
indicated that β-CD complex with CUR with
an apparent formation constant of 1.09 × 10-8mol-1dm-3.
Based on the data obtained by methylthiazole tetrazolium (MTT), β-CD showed that not only did it
enhanced Curcumin delivery, but it also improved and promoted the
anti-proliferative effect of CUR during the complexation
rather than CUR alone on the MCF-7 human breast
cancer cells at 24 h incubation period with IC50 lower
than that of Curcumin alone. The toxicities of the β-CD-CUR towards MCF-7
cells were also compared to the free tamoxifen, Curcumin and β-CD.
This study provides a preliminary toxicity evaluation based on β-CD-CUR inclusion complex as potential delivery system towards the
selected cancer cells.
Keywords: β-cyclodextrin; Curcumin;
cytotoxicity; inclusion complex
ABSTRAK
Perkembangan dan penggunaan
pengangkut ubat
organik dalam sistem
pengangkutan ubat
(DDSs)
dengan lebih
berkesan dan kesan
sampingan yang sedikit
masih menjadi cabaran
besar dalam
penyelidikan sains dan perubatan moden.
Objektif kajian
ini adalah untuk
menilai keupayaan
β-siklodekstrin (β-CD)
sebagai pengangkut ubat untuk merangkumkan
Kurkumin (CUR), satu kemoterapeutik
yang mempunyai kelarutan
air dan ketersediaan
biologi rendah agar dapat membentuk kompleks inklusi dengan cara menguli untuk
meningkatkan penghantarannya
ke sel
kanser. Kaedah
pencirian seperti inframerah transformasi Fourier (FTIR),
1H
Resonans Magnet Nukleus
(1H
NMR),
pembelauan sinar-X
(XRD),
Mikroskop Elektron
Pengimbas (SEM) dan
Analisis -Gravimetrik
Terma (TGA) telah
digunakan untuk membuktikan pembentukan kompleks inklusif dengan gelang aromatik
CUR
telah dirangkumkan
dalam rongga
hidrofobik β-CD. Penyerapan ultra-lembayung (UV) menunjukkan
kompleks β-CD dengan CUR mempunyai
pembentukan pemalar
ketara 1.09 × 10-8 mol-1 dm-3.
Berdasarkan data methylthiazole
tetrazolium (MTT), β-CD bukan
sahaja meningkatkan
pengangkutan Kurkuminmalahan
menambah baik dan
mempromosikan kesan
anti-proliferatifnya semasa kompleks pada MCF-7
sel kanser
payudara manusia dalam tempoh inkubasi
24 jam dengan IC50 lebih
rendah daripada Kurkumin sahaja. Toksiksiti β-CD-CUR terhadap
sel MCF-7 juga dibandingkan
dengan tamoxifen, Kurkumin
dan β-CD asli. Kajian ini berjaya menyediakan
penilaian ketoksikan
awal berdasarkan rangkuman kompleks β-CD-CUR
sebagai sistem
pengangkutan ubat
yang berpotensi ke arah
sel-sel kanser
yang dipilih.
Kata kunci: β-siklodekstrin;
kesitotoksikan ; Kurkumin; rangkuman kompleks
RUJUKAN
Bar-Sela, G., Epelbaum,
R. & Schaffer, M. 2010. Curcumin as an
anti-cancer agent: Review of the gap between basic and clinical applications. Current
Medicinal Chemistry 17: 190-197.
Danhier, F., Olivier, F. & Véronique, P. 2010. To exploit the tumor microenvironment:
Passive and active tumor targeting of nanocarriers for anti-cancer drug gelivery. Journal of
Controlled Release 148(2): 135-146.
Fermeglia, M., Ferrone,
M., Lodi, A. & Pricl, S. 2003. Host-guest
inclusion complexes between anticancer drugs and β-Cyclodextrin:
Computational studies. Carbohydrate Polymers 53(1): 15-44.
Gafner, S., Sang, K.L., Muriel,
C., Sophie, B., Laurent, V., Serge, L., Rajendra,
G.M., Charles, W.B. & John, M.P. 2004. Biologic evaluation of curcumin and structural derivatives in
cancer chemoprevention model systems. Phytochemistry 65: 2849-2859.
Gómez-Galván, F., Pérez-Álvarez, L., Janire, M., Álvarez- Bautista, A., Joana, P., Catarina, M.D.,
Ruiz-Rubio, L., Vila-Vilela, J.L. & Luis, M.L.
2016. Preparation and characterization of soluble
branched ionic β-Cyclodextrins and their
inclusion complexes with triclosan. Carbohydrate
Polymers 142: 149-157.
Holder, G.M., Plummer, J.L. & Ryan, A.J. 1978. The metabolism and excretion of curcumin (1,7-Bis-(4-Hydroxy-3- Methoxyphenyl)-1,6-Heptadiene-3,5-Dione) in the rat. Xenobiotica; the Fate of Foreign Compounds in
Biological Systems 8(12): 761-768.
Jabbarzadeh, K.P., Asmah, R., Patimah,
I. & Kingm, H.L. 2014. Targets and mechanisms of berberine, a
natural drug with potential to treat cancer with special focus on breast
cancer. European Journal of Pharmacology 740: 584-595.
Jahed, V., Ali, Z., Khalegh, B.A. &
Mohammad, S.H. 2014. NMR (1H,
ROESY) spectroscopic and molecular modelling investigations of supramolecular
complex of β-Cyclodextrin and curcumin. Food
Chemistry 165: 241-246.
Jha, N.N., Dhiman, G., Subhadeep,
D., Arunagiri, A., Reeba,
S.J., Pradeep, K.S., Narasimham, A., Irishi, N.N.N. & Samir, K.M. 2016. Effect of curcumin analogs Onα-Synuclein aggregation and cytotoxicity. Scientific
Reports 6: 28511.
Khan, M.A., Zafaryab, M., Mehdi, S.H.,
Ahmad, I. & Rizvi, M.M. 2016. Characterization and anti-proliferative activity of curcumin loaded chitosan
nanoparticles in cervical cancer. International Journal of Biological
Macromolecules 93(Part A): 242-253.
Kuntz, I.D., Gasparro, F.P., Johnston,
M.D. & Taylor, R.P. 1968. Molecular
interactions and the benesi-hildebrand equation. Journal of the American Chemical Society 90(18): 4778- 4781.
Li, L., Fadi, S.B. & Razelle, K. 2005. Liposome-encapsulated curcumin. Cancer 104(6):
1322-1331.
Liu, Z., Yusheng, S., Luqing, R., Yi, H., Yuepiao, C., Qiaoyou, W., Xueqian, S., Xiaokun, L., Guang, L. & Yi,
W. 2013. Evaluation of a curcumin analog as an anti-cancer
agent inducing ER stress-mediated apoptosis in non-small cell lung cancer
cells. BMC Cancer 13(1): 494.
Mangolim, C.S., Cristiane,
M., Ana, C.N., Francielle, S., Mauro, L.B., Antônio, M.N. & Graciette, M.
2014. Curcumin- β-Cyclodextrin inclusion
complex: Stability, solubility, characterisation by
FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food
application. Food Chemistry 153: 361-370.
Memisoglu-Bilensoy, E., Vural, I., Bochot,
A., Renoir, J.M., Duchene, D. & Hincal, A.A.
2005. Tamoxifen citrate loaded amphiphilic β-Cyclodextrin nanoparticles: In vitro characterization and cytotoxicity. Journal of
Controlled Release 104(3): 489-496.
Mohamad, S., Hemavathy, S., Muggundha, R., Tilagam, M., Kumuthini, C. & Puvaneswary,
S. 2011. Conventional study on novel dicationic ionic liquid inclusion with β-Cyclodextrin. International Journal of Molecular Sciences 12: 6329-6345.
Rachmawati, H., Citra, A.E. & Rachmat, M.
2013. Molecular inclusion complex of curcumin–β-Cyclodextrin nanoparticle to enhance curcumin skin
permeability from hydrophilic matrix gel. AAPS PharmSciTech 14(4): 1303-1312.
Raoov, M., Mohamad, S. & Abas, M.R. 2013. Removal of 2,4-Dichlorophenol using cyclodextrin-ionic liquid polymer as a macroporous material: Characterization, adsorption isotherm, kinetic study, thermodynamics. Journal of Hazardous Materials 263: 501-516.
Salem, M., Ying, X., Alison, A. & Elizabeth, R.G. 2015. RSC advances magnetite particles for targeted drug delivery. RSC
Advances 5: 37521-37532.
Sambasevam, K.P., Mohamad, S., Norazilawati, M.S. & Ismail, N.A. 2013. Synthesis and characterization of the inclusion complex of β-Cyclodextrin and azomethine. International Journal of Molecular Sciences 14: 3671-3682.
Sou, K., Shunsuke, I., Shinji, T. & Eishun, T. 2008. Loading of curcumin into macrophages using lipid-based
nanoparticles. International Journal of Pharmaceutics 352(1-2):
287-293.
Subramaniam, P., Mohamad, S. & Yatimah, A.
2010. Synthesis and characterization of the inclusion
complex of dicationic ionic liquid and β-Cyclodextrin. International Journal of Molecular
Sciences 11(10): 3675-3685.
Ucar, E., Serap, T., Cigdem,
I., Ayfer, Y.K., Medine,
E.I., Kadir, A., Yasemin,
P., Elvan, B.S.B. & Perihan, U. 2017. Synthesis, characterization and radiolabeling of folic acid
modified nanostructured lipid carriers as a contrast agent and drug delivery
system. Applied Radiation and Isotopes 119: 72-79.
Wan Omar, W.A., Azhar, N.A., Nurdianah, H.F. & Nik Mohamed Kamal, N.N.S. 2016. Bee pollen extract of Malaysian stingless bee enhances the effect
of cisplatin on breast cancer cell lines. Asian Pacific Journal of Tropical
Biomedicine 6(3): 265-269.
Wang, H.Y., Juan, H. & Xia, G.F. 2007. Spectroscopic study of orange G-β-Cyclodextrin complex and its analytical application. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 66(3): 578-585.
Wilken, R., Mysore, S.V., Marilene, B.W.
& Eri, S.S. 2011. Curcumin: A review of anti-cancer properties and therapeutic activity in head
and neck squamous cell carcinoma. Molecular Cancer 10(1): 12.
Williams III, R.O., Vorapann, M. & Mongkol, S. 1998. Characterization of an inclusion complex of cholesterol and hydroxypropyl-β-Cyclodextrin. European Journal of Pharmaceutics and Biopharmaceutics 46(3): 355-360.
Yallapu, M.M., Meena, J. & Subhash, C.C. 2010. β-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids
and Surfaces B: Biointerfaces79(1): 113-125.
Yu, H. & Qingrong, H. 2010. Enhanced in vitro anti-cancer activity of curcumin
encapsulated in hydrophobically modified starch. Food
Chemistry 119(2): 669-674.
Zhang,
J.Q., Di, W., Kun, M.J., Da, Z., Xi, Z., Chun, P.W., Hong, Y.Z., Xiao, G.X., Yi,
J. & Jun, L. 2015. Preparation, spectroscopy
and molecular modelling studies of the inclusion complex of cordycepin with cyclodextrins. Carbohydrate Research 406: 55-64.
*Pengarang
untuk surat-menyurat:
muggundha@um.edu.my