Design and Synthesis of a Novel Dendrosome and a PEGylated PAMAM Dendrimer Nanocarrier to Improve the Anticancer effect of Turmeric (Curcuma longa) Curcumin

Authors
M. Sadeghizadeh 1
V. Erfani-Moghadam 2
A. Nomani 3
F. Najafi 4
Y. Yazdani 5
M. Sadeghizadeh 1
1 Department of Genetic, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2 Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
3 Department of Pharmaceutics, Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
4 Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran
5 Infectious Diseases Research Center and Laboratory Science Research Center, Golestan University of Medical Sciences, Gorgan, Iran
Abstract
Objective: In recent decades, the anticancer effect of curcumin has been proven by several studies. Curcumin affects multiple cell signaling pathways and prevents cell proliferation, invasion, metastasis and angiogenesis. However, the aqueous solubility of curcumin and its bioavailability are very low which restricts its anticancer properties. In this research, we have synthesized a monomethoxy poly (ethylene glycol)-Oleate (mPEG-OA) di-block copolymer and used a surface PEGylated poly (amidoamine) (PAMAM) dendrimer to improve bioavailability of curcumin in cancer cells. Methods: Thecritical micelle concentration (CMC) of mPEG-OA, drug loading efficiencies, and cytotoxicity in the human glioblastoma cell line (U87MG) of all the prepared nanodevices were thoroughly investigated. Results: Atomic force microscopy (AFM) and dynamic light scattering (DLS) studies have shown that mPEG-OA have two common nanostructures, micelles and polymerosomes. mPEG-OA micelles had a very low CMC (0.03 g/l). The IC50 of free curcumin (0.01 methanol solution) was 48 μM, curcumin-loaded mPEG-OA was 24 μM , and curcumin-loaded PAMAM dendrimer was 13 μM. Moreover, the PEGylated PAMAM was non-cytotoxic. Conclusion: The results indicated that by using these nanocarriers, the bioavailability of curcumin significantly increased compared to free curcumin. Overall, this research revealed that these curcumin nanocarriers could be considered as appropriate drug delivery systems for curcumin delivery in cancer cells.

Keywords

[1]     Bharali DJ, Khalil M, Gurbuz M, Simone TM, Mousa SA. Nanoparticles and cancer therapy: a concise review with emphasis on dendrimers. Int J Nanomedicine 2009; 4: 1-7.
[2]     Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett 2008; 267(1): 133-64.
[3]     Li Z, Percival SS, Bonard S, Gu L. Fabrication of nanoparticles using partially purified pomegranate ellagitannins and gelatin and their apoptotic effects. Mol Nutr Food Res 2011; 55(7): 1096-103.
[4]     Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 1997; 15(12): 1867-76.
[5]     Joe B, Vijaykumar M, Lokesh BR. Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr 2004; 44(2): 97-111.
[6]     Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer 2005; 41(13): 1955-68.
[7]     Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol 2008; 75(4): 787-809.
[8]     Yallapu MM, Jaggi M, Chauhan SC. Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discov Today 2012; 17(1-2): 71-80.
[9]     Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007; 4(6): 807-18.
[10] D'Emanuele A, Attwood D. Dendrimer-drug interactions. Adv Drug Deliv Rev 2005; 57(15): 2147-62.
[11] Wiener EC, Konda S, Shadron A, Brechbiel M, Gansow O. Targeting dendrimer-chelates to tumors and tumor cells expressing the high-affinity folate receptor. Invest Radiol 1997; 32(12): 748-54.
[12] Patri AK, Kukowska-Latallo JF, Baker JR Jr. Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Adv Drug Deliv Rev 2005; 57(15): 2203-14.
[13] Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener JW, Meijer EW, Paulus W, Duncan R. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J Control Release 2000; 65(1-2): 133-48.
[14] Tahmasebi Mirgani M, Sadeghizadeh M, Najafi F, Mowla SJ. Dendrosomal curcumin induced apoptosis by suppression of pluripotency genes in 5637 bladder cancer cells. Modares Journal of Medical Sciences: Pathobiology 2013; 16(1): 23-39. (Persian)
[15] Sahu A, Bora U, Kasoju N, Goswami P. Synthesis of novel biodegradable and self-assembling methoxy poly(ethylene glycol)-palmitate nanocarrier for curcumin delivery to cancer cells. Acta Biomater 2008; 4(6): 1752-61.
[16] Gou M, Men K, Shi H, Xiang M, Zhang J, Song J, Long J, Wan Y, Luo F, Zhao X, Qian Z. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo. Nanoscale 2011; 3(4): 1558-67.
[17] Darvishi MH, Nomani A, Amini M, Shokrgozar MA, Dinarvand R. Novel biotinylated chitosan-graft-polyethyleneimine copolymer as a targeted non-viral vector for anti-EGF receptor siRNA delivery in cancer cells. Int J Pharm 2013; 456(2): 408-16.
[18] Luo D, Kraig H, Belcheva N, Han E, Saltzman WM. Poly(ethylene glycol)-conjugated PAMAM dendrimer for biocompatible, high-efficiency DNA delivery. Macromolecules 2002, 35(9): 3456-62.
[19] Zhu S, Hong M, Zhang L, Tang G, Jiang Y, Pei Y. PEGylated PAMAM dendrimer-doxorubicin conjugates: in vitro evaluation and in vivo tumor accumulation. Pharm Res 2010; 27(1): 161-74.
[20] Boas U, Christensen JB, Heegaard PMH. Dendrimers in medicine and biotechnology: new molecular tools. 2006; Available at: http://www.springer.com/chemistry/organic+chemistry/book/978-0-85404-852-6
[21] Liu M, Kono K, Frechet JMJ. Water-soluble dendrimer-poly(ethylene glycol) starlike conjugates as potential drug carriers. J Polym Sci A Polym Chem 1999, 37(17): 3492-503.
[22] Hourani R, Kakkar A. Advances in the elegance of chemistry in designing dendrimers. Macromol Rapid Commun 2010; 31(11): 947-74.
[23] Gillies ER, Dy E, Fréchet JM, Szoka FC. Biological evaluation of polyester dendrimer: poly(ethylene oxide) "bow-tie" hybrids with tunable molecular weight and architecture. Mol Pharm 2005; 2(2): 129-38.
Pathobiology Reserach
Volume 17, Issue 1
April 2014
Pages 63-77