Curcumin Nanoemulsion: Evaluation of Stability and Anti-Cancer Activity In Vitro

Article Preview

Abstract:

Curcumin is a phytochemical compound extracted from the rhizomes of the plant Curcuma longa and shows intrinsic anti-cancer properties. Its medical application remains limited due to its extremely low water solubility and bioavailability. Addressing this problem, drug delivery systems based on nano-scale technology have emerged. Among the advanced techniques, the self-nano-emulsifying drug delivery system (SNEDDS) has been considered as an ideal method to enhance the oral absorption and bioavailability of poorly water-soluble drugs. The objectives of present study are to prepare a formulation of nanoemulsion containing curcuminoids of natural origin, assess its micro properties, stabilities and evaluate the in vitro cytotoxic activity against some cancer cells using tetrazolium dye MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo- lium bromide] (MTT assay). Measurement results showed that the curcumin nanoemulsion was successfully synthesized with typical mean droplet sizes from 9 to 11 nm, and revealed an excellent stability over time. Curcumin in a nanoemulsion was more stable than unencapsulated curcumin. In vitro experiments on cytotoxic activities against Hela, HepG2 and H460 cancer cell lines indicated that the prepared curcumin nanoemulsion effectively inhibited the growth of all three cell lines with IC50 values of 8.6 µM, 14.5 µM and 5.3 µM respectively. Results of this study suggest that curcumin nanoemulsion can be considered as novel and promising chemo-preventive and therapeutic drug in treatment of cancer, and it may supply some useful ideas in developing anticancer drugs for further in vivo studies.

You might also be interested in these eBooks

Info:

Periodical:

Pages:

21-37

Citation:

Online since:

November 2020

Export:

Price:

* - Corresponding Author

[1] A.E. Krausz, B.L. Adler, V. Cabral, M. Navati, J. Doerner, R.A. Charafeddine, D. Chandra, H. Liang, L. Gunther, A. Clendaniel, S. Harper, J.M. Friedman, J.D. Nosanchuk, A.J. Friedman, Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent, Nanomedicine Nanotechnology, Biol. Med. 11 (2015) 195–206.

DOI: 10.1016/j.nano.2014.09.004

Google Scholar

[2] S. Mangalathillam, N.S. Rejinold, A. Nair, V.K. Lakshmanan, S. V. Nair, R. Jayakumar, Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route, Nanoscale. 4 (2012) 239–250.

DOI: 10.1039/c1nr11271f

Google Scholar

[3] M.K. Das, R. Kumar, Development of curcumin nanoniosomes for skin cancer chemoprevention, Int. J. ChemTech Res. 7 (2015) 747–754.

Google Scholar

[4] J. Wang, H. Wang, R. Zhu, Q. Liu, J. Fei, S. Wang, Anti-inflammatory activity of curcumin-loaded solid lipid nanoparticles in IL-1β transgenic mice subjected to the lipopolysaccharide-induced sepsis, Biomaterials. 53 (2015) 475–483.

DOI: 10.1016/j.biomaterials.2015.02.116

Google Scholar

[5] R.K. Maheshwari, A.K. Singh, J. Gaddipati, R.C. Srimal, Multiple biological activities of curcumin: A short review, Life Sci. 78 (2006) 2081–(2087).

DOI: 10.1016/j.lfs.2005.12.007

Google Scholar

[6] P. Basnet, N. Skalko-Basnet, Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment, Molecules. 16 (2011) 4567–4598.

DOI: 10.3390/molecules16064567

Google Scholar

[7] B.B. Aggarwal, K.B. Harikumar, Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases, Int. J. Biochem. Cell Biol. 41 (2009) 40–59.

DOI: 10.1016/j.biocel.2008.06.010

Google Scholar

[8] K. Bairwa, J. Grover, M. Kania, S.M. Jachak, Recent developments in chemistry and biology of curcumin analogues, RSC Adv. 4 (2014) 13946–13978.

DOI: 10.1039/c4ra00227j

Google Scholar

[9] T. Ahmed, A.H. Gilani, Therapeutic potential of turmeric in Alzheimer's disease: Curcumin or curcuminoids?, Phyther. Res. 28 (2014) 517–525.

DOI: 10.1002/ptr.5030

Google Scholar

[10] N.K. Vishvakarma, Novel antitumor mechanisms of curcumin: Implication of altered tumor metabolism, reconstituted tumor microenvironment and augmented myelopoiesis, Phytochem. Rev. 13 (2014) 717–724.

DOI: 10.1007/s11101-014-9364-2

Google Scholar

[11] M.H. Teiten, S. Eifes, M. Dicato, M. Diederich, Curcumin-the paradigm of a multi-target natural compound with applications in cancer prevention and treatment, Toxins (Basel). 2 (2010) 128–162.

DOI: 10.3390/toxins2010128

Google Scholar

[12] A. Goel, A.B. Kunnumakkara, B.B. Aggarwal, Curcumin as Curecumin,: From kitchen to clinic, Biochem. Pharmacol. 75 (2008) 787–809.

DOI: 10.1016/j.bcp.2007.08.016

Google Scholar

[13] V. Badmaev, Curcuminoids from Curcuma longa in Disease Prevention and Treatment, in: R. Cooper and F. Kronenberg (Ed.), Bot. Med. From Bench to Bedside, 1st ed., Mary Ann Liebert Inc., New Rochelle, NY, USA, 2009: p.109–138.

Google Scholar

[14] T.T.H. Nguyen, J. Si, C. Kang, B. Chung, D. Chung, D. Kim, Facile preparation of water soluble curcuminoids extracted from turmeric (Curcuma longa L.) powder by using steviol glucosides, Food Chem. 214 (2017) 366–373.

DOI: 10.1016/j.foodchem.2016.07.102

Google Scholar

[15] H.H. Tønnesen, M. Másson, T. Loftsson, Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: Solubility, chemical and photochemical stability, Int. J. Pharm. 244 (2002) 127–135.

DOI: 10.1016/s0378-5173(02)00323-x

Google Scholar

[16] A. Shah, V. Thakkar, M. Gohel, L. Baldaniya, T. Gandhi, Optimization of Self Micro Emulsifying Drug Delivery System Containing Curcumin and Artemisinin Using D-Optimal Mixture Design, Saudi J. Med. Pharm. Sci. 3 (2017) 388–398.

Google Scholar

[17] Y. bin Guan, S. yao Zhou, Y. qiong Zhang, J. le Wang, Y. dong Tian, Y. yan Jia, Y. jun Sun, Therapeutic effects of curcumin nanoemulsions on prostate cancer, J. Huazhong Univ. Sci. Technol. - Med. Sci. 37 (2017) 371–378.

DOI: 10.1007/s11596-017-1742-8

Google Scholar

[18] D.M. Dhumal, P.R. Kothari, R.S. Kalhapure, K.G. Akamanchi, Self-microemulsifying drug delivery system of curcumin with enhanced solubility and bioavailability using a new semi-synthetic bicephalous heterolipid: In vitro and in vivo evaluation, RSC Adv. 5 (2015) 90295–90306.

DOI: 10.1039/c5ra18112g

Google Scholar

[19] C.D. Lao, M.T. Ruffin IV, D. Normolle, D.D. Heath, S.I. Murray, J.M. Bailey, M.E. Boggs, J. Crowell, C.L. Rock, D.E. Brenner, Dose escalation of a curcuminoid formulation, BMC Complement. Altern. Med. 6 (2006) 4–7.

DOI: 10.1186/1472-6882-6-10

Google Scholar

[20] M. Gera, N. Sharma, M. Ghosh, D.L. Huynh, S.J. Lee, T. Min, T. Kwon, D.K. Jeong, Nanoformulations of curcumin: An emerging paradigm for improved remedial application, Oncotarget. 8 (2017) 66680–66698.

DOI: 10.18632/oncotarget.19164

Google Scholar

[21] H. Yavarpour-Bali, M. Pirzadeh, M. Ghasemi-Kasman, Curcumin-loaded nanoparticles: A novel therapeutic strategy in treatment of central nervous system disorders, Int. J. Nanomedicine. 14 (2019) 4449–4460.

DOI: 10.2147/ijn.s208332

Google Scholar

[22] A.A. Date, N. Desai, R. Dixit, M. Nagarsenker, Self-nanoemulsifying drug delivery systems: Formulation insights, applications and advances, Nanomedicine. 5 (2010) 1595–1616.

DOI: 10.2217/nnm.10.126

Google Scholar

[23] O. Sonneville-Aubrun, J.-T. Simonnet, F. L'Alloret, Nanoemulsions: a new vehicle for skincare products, Adv. Colloid Interface Sci. 108–109 (2004) 145–149.

DOI: 10.1016/j.cis.2003.10.026

Google Scholar

[24] M.A. Altamimi, M. Kazi, M. Hadi Albgomi, A. Ahad, M. Raish, Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure, Drug Dev. Ind. Pharm. 45 (2019) 1073–1078.

DOI: 10.1080/03639045.2019.1593440

Google Scholar

[25] T. Jiang, W. Liao, C. Charcosset, Recent advances in encapsulation of curcumin in nanoemulsions: A review of encapsulation technologies, bioaccessibility and applications, Food Res. Int. 132 (2020) 109035.

DOI: 10.1016/j.foodres.2020.109035

Google Scholar

[26] P. Walstra, Principles of emulsion formation, Chem. Eng. Sci. 48 (1993) 333–349.

Google Scholar

[27] N.H. Shah, M.T. Carvajal, C.I. Patel, M.H. Infeld, A.W. Malick, Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs, Int. J. Pharm. 106 (1994) 15–23.

DOI: 10.1016/0378-5173(94)90271-2

Google Scholar

[28] R.N. Gursoy, S. Benita, Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs, Biomed. Pharmacother. 58 (2004) 173–182.

DOI: 10.1016/j.biopha.2004.02.001

Google Scholar

[29] S. Nazzal, I.I. Smalyukh, O.D. Lavrentovich, M.A. Khan, Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system (SNEDDS) of ubiquinone: Mechanism and progress of emulsion formation, Int. J. Pharm. 235 (2002) 247–265.

DOI: 10.1016/s0378-5173(02)00003-0

Google Scholar

[30] H.H. Tønnesen, J. Karlsen, Studies on curcumin and curcuminoids, Zeitschrift Für Leb. Und Forsch. 180 (1985) 132–134.

Google Scholar

[31] S.D. Hardiningtyas, R. Wakabayashi, R. Ishiyama, Y. Owada, M. Goto, N. Kamiya, Enhanced potential of therapeutic applications of curcumin using solid-in-water nanodispersion technique, J. Chem. Eng. Japan. 52 (2019) 138–143.

DOI: 10.1252/jcej.18we060

Google Scholar

[32] K.K. Gupta, S.S. Bharne, K. Rathinasamy, N.R. Naik, D. Panda, Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding, FEBS J. 273 (2006) 5320–5332.

DOI: 10.1111/j.1742-4658.2006.05525.x

Google Scholar

[33] L. Ding, S. Ma, H. Lou, L. Sun, M. Ji, Synthesis and biological evaluation of curcumin derivatives with water-soluble groups as potential antitumor agents: An in vitro investigation using tumor cell lines, Molecules. 20 (2015) 21501–21514.

DOI: 10.3390/molecules201219772

Google Scholar

[34] S. Banerjee, P. Prasad, A. Hussain, I. Khan, P. Kondaiah, A.R. Chakravarty, Remarkable photocytotoxicity of curcumin in HeLa cells in visible light and arresting its degradation on oxovanadium(IV) complex formation, Chem. Commun. 48 (2012) 7702–7704.

DOI: 10.1039/c2cc33576j

Google Scholar

[35] H.Y. Zhang, C. yong Sun, M. Adu-Frimpong, J. nan Yu, X. ming Xu, Glutathione-sensitive PEGylated curcumin prodrug nanomicelles: Preparation, characterization, cellular uptake and bioavailability evaluation, Int. J. Pharm. 555 (2019) 270–279.

DOI: 10.1016/j.ijpharm.2018.11.049

Google Scholar

[36] K.C. Kim, S.H. Baek, C. Lee, Curcumin-induced downregulation of Axl receptor tyrosine kinase inhibits cell proliferation and circumvents chemoresistance in non-small Lung cancer cells, Int. J. Oncol. 47 (2015) 2296–2303.

DOI: 10.3892/ijo.2015.3216

Google Scholar

[37] A.R.M.R. Amin, A. Haque, M.A. Rahman, Z.G. Chen, F.R. Khuri, D.M. Shin, Curcumin induces apoptosis of upper aerodigestive tract cancer cells by targeting multiple pathways, PLoS One. 10 (2015) 1–11.

DOI: 10.1371/journal.pone.0124218

Google Scholar

[38] Z. Liu, Y. Sun, L. Ren, Y. Huang, Y. Cai, Q. Weng, X. Shen, X. Li, G. Liang, Y. Wang, Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells, BMC Cancer. 13:494 (2013).

DOI: 10.1186/1471-2407-13-494

Google Scholar

[39] S. Man, L. Zhang, J. Cui, L. Yang, L. Ma, W. Gao, Curcumin enhances the anti-cancer effects of Paris Saponin II in lung cancer cells, Cell Prolif. 51(4) (2018): e12458.

DOI: 10.1111/cpr.12458

Google Scholar