Volume 10, Issue 3 (2019)
JMBS 2019, 10(3): 491-502 |
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Kianamiri S, Dinari A, Nomani A R, Sadeghizadeh M, Mardi M, Daraei B. Fabrication and Assessment of Novel Nano-Drug Delivery System Prepared by Conjugation of Dendrimer– Curcumin and Study of its Effect on Cancerous and Normal Cells. JMBS 2019; 10 (3) :491-502
URL: http://biot.modares.ac.ir/article-22-22991-en.html
URL: http://biot.modares.ac.ir/article-22-22991-en.html
1- Nanobiotechnology Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran
2- Pharmaceutical Biomaterials Department, Pharmacy Faculty, Zanjan University of Medical Sciences, Zanjan, Iran
3- Genetics Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran, Tarbiat Modares University, Nasr Bridge, Jalal-Al-Ahmad Highway, Tehran, Iran , sadeghma@modares.ac.ir
4- Agricutural Biotechnology Research Institute of Iran, Karaj, Iran
5- Toxicology & Pharmacology Department, Pharmacy Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2- Pharmaceutical Biomaterials Department, Pharmacy Faculty, Zanjan University of Medical Sciences, Zanjan, Iran
3- Genetics Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran, Tarbiat Modares University, Nasr Bridge, Jalal-Al-Ahmad Highway, Tehran, Iran , sadeghma@modares.ac.ir
4- Agricutural Biotechnology Research Institute of Iran, Karaj, Iran
5- Toxicology & Pharmacology Department, Pharmacy Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract: (3905 Views)
Antioxidant, anticancer, anti-inflammatory, and anti-microbial activities are evidences for the invaluable benefit of this herbal extract in human health and therapy. The anticancer effect of curcumin is due to the targeting of a wide range of cellular and molecular pathways involved in cancer progression. However, the limited solubility, low bioavailability and rapid metabolism of curcumin have a serious negative impact on its therapeutic application. In this research, a nano-carrier with appropriate delivery features, prepared through the conjugation of curcumin to the surface of a polyamidoamine dendrimer at generation 4 (PAMAM). The structure of the synthesized dendrimeric curcumin was confirmed by FT-IR and 1H-NMR methods. The particles size and zeta potential were measured by Zetasizer. The loading rate of curcumin molecules on nano-carrier investigated and the cell viability, intracellular reactive oxygen species and induction of apoptosis were evaluated using MTT assay and flow cytometry technique in the follows. The results of this study showed that the prepared dendrimeric curcumin had a hydrodynamic diameter of about 100 nm. The results show that the rate of curcumin loading on this nanostructure system was about four curcumin molecules per each dendrimer. Cell experiments indicated that the toxicity, cellular reactive oxygen species (ROS), and apoptosis caused by dendrimeric nano-carrier were higher than free curcumin. Better performance of dendrimer-Nano-carrier was been through the improvement of physicochemical properties and increased curcumin solubility. Overall, it seems that the prepared dendrimeric curcumin is able to significantly improve the delivery of hydrophobic drugs on cancerous cells.
Article Type: Original Research |
Subject:
Pharmaceutical Biotechnology
Received: 2018/07/11 | Accepted: 2018/08/18 | Published: 2019/09/21
Received: 2018/07/11 | Accepted: 2018/08/18 | Published: 2019/09/21
References
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. [Link] [DOI:10.2147/IJN.S4241]
2. Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008;269(2):199-225. [Link] [DOI:10.1016/j.canlet.2008.03.009]
3. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1-75. [Link] [DOI:10.1007/978-0-387-46401-5_1]
4. Bonifácio BV, Silva PB, Ramos MA, Negri KM, Bauab TM, Chorilli M. Nanotechnology-based drug delivery systems and herbal medicines: a review. Int J Nanomedicine. 2014;9:1-15. [Link] [DOI:10.2147/IJN.S52634]
5. Thilakarathna SH, Rupasinghe HP. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients. 2013;5(9):3367-87. [Link] [DOI:10.3390/nu5093367]
6. Mignani S, Rodrigues J, Tomas H, Zablocka M, Shi X, Caminade AM, et al. Dendrimers in combination with natural products and analogues as anti-cancer agents. Chem Soc Rev. 2018;47(2):514-32. [Link] [DOI:10.1039/C7CS00550D]
7. Wu LP, Ficker M, Christensen JB, Trohopoulos PN, Moghimi SM. Dendrimers in medicine: therapeutic concepts and pharmaceutical challenges. Bioconjug Chem. 2015;26(7):1198-211. [Link] [DOI:10.1021/acs.bioconjchem.5b00031]
8. Mintzer MA, Grinstaff MW. Biomedical applications of dendrimers: a tutorial. Chem Soc Rev. 2011;40(1):173-90. [Link] [DOI:10.1039/B901839P]
9. Dufes C, Uchegbu IF, Schätzlein AG. Dendrimers in gene delivery. Adv Drug Deliv Rev. 2005;57(15):2177-202. [Link] [DOI:10.1016/j.addr.2005.09.017]
10. Jain K, Kesharwani P, Gupta U, Jain N. Dendrimer toxicity: Let's meet the challenge. Int J Pharm. 2010;394(1-2):122-42. [Link] [DOI:10.1016/j.ijpharm.2010.04.027]
11. Nomani A, Haririan I, Rahimnia R, Fouladdel S, Gazori T, Dinarvand R, et al. Physicochemical and biological properties of self-assembled antisense/poly (amidoamine) dendrimer nanoparticles: the effect of dendrimer generation and charge ratio. Int J Nanomedicine. 2010;5:359-69. [Link] [DOI:10.2147/IJN.S9070]
12. Tahmasebi Birgani M, Erfani-Moghadam V, Babaei E, Najafi F, Zamani M, Shariati M, et al. Dendrosomal nano-curcumin; The novel formulation to improve the anticancer properties of curcumin. Prog Biol Sci. 2015;5(2):143-58. [Link]
13. Erfani-Moghadam V, Nomani A, Zamani M, Yazdani Y, Najafi F, Sadeghizadeh M. A novel diblock of copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells. Int J Nanomedicine. 2014;9:5541-54. [Link] [DOI:10.2147/IJN.S63762]
14. Dinari A, Moghadam TT, Abdollahi M, Sadeghizadeh M. Synthesis and characterization of a Nano-Polyplex system of GNRs-PDMAEA-pDNA: an inert self-catalyzed degradable carrier for facile gene delivery. Sci Rep. 2018;8(8112):1-12. [Link] [DOI:10.1038/s41598-018-26260-4]
15. Naksuriya O, Okonogi S, Schiffelers RM, Hennink WE. Curcumin nanoformulations: a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials. 2014;35(10):3365-83. [Link] [DOI:10.1016/j.biomaterials.2013.12.090]
16. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": from kitchen to clinic. Biochem Pharmacol. 2008;75(4):787-809. [Link] [DOI:10.1016/j.bcp.2007.08.016]
17. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11(3):495-510. [Link] [DOI:10.1208/s12248-009-9128-x]
18. Lim J, Simanek EE. Synthesis of water-soluble dendrimers based on melamine bearing 16 paclitaxel groups. Org Lett. 2008;10(2):201-4. [Link] [DOI:10.1021/ol7024907]
19. Shukla RK, Sharma V, Pandey AK, Singh S, Sultana S, Dhawan A. ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells. Toxicol In Vitro. 2011;25(1):231-41. [Link] [DOI:10.1016/j.tiv.2010.11.008]
20. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Ann Rev Pathol. 2010;5:253-95. [Link] [DOI:10.1146/annurev.pathol.4.110807.092250]
21. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8(7):579-91. [Link] [DOI:10.1038/nrd2803]
22. Sullivan LB, Chandel NS. Mitochondrial reactive oxygen species and cancer. Cancer Metab. 2014;2(1):17. [Link] [DOI:10.1186/2049-3002-2-17]
23. Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, et al. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol. 2008;76(11):1590-611. [Link] [DOI:10.1016/j.bcp.2008.08.008]
24. Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. J Parenter Enteral Nutr. 2006;30(1):45-51. [Link] [DOI:10.1177/014860710603000145]
25. López‐Lázaro M. Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Mol Nutr Food Res. 2008;52 Suppl 1:S103-27. [Link] [DOI:10.1002/mnfr.200700238]
26. Wallace DC. Mitochondria and cancer: Warburg addressed. Cold Spring Harb Symp Quant Biol. 2005;70:363-74. [Link] [DOI:10.1101/sqb.2005.70.035]
27. Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nat Rev Drug Discov. 2010;9(6):447-64. [Link] [DOI:10.1038/nrd3137]
28. Duvoix A, Morceau F, Delhalle S, Schmitz M, Schnekenburger M, Galteau MM, et al. Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1 inhibition. Biochem Pharmacol. 2003;66(8):1475-83. [Link] [DOI:10.1016/S0006-2952(03)00501-X]
29. Thangapazham RL, Sharma A, Maheshwari RK. Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J. 2006;8(3):E443-9. [Link] [DOI:10.1208/aapsj080352]
30. Hsu CC, Tseng LM, Lee HC. Role of mitochondrial dysfunction in cancer progression. Exp Biol Med. 2016;241(12):1281-95. [Link] [DOI:10.1177/1535370216641787]
31. Wallace DC. Mitochondrial diseases in man and mouse. Science. 1999;283(5407):1482-8. [Link] [DOI:10.1126/science.283.5407.1482]
32. Thayyullathil F, Chathoth S, Hago A, Patel M, Galadari S. Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and-independent apoptosis in L929 cells. Free Radic Biol Med. 2008;45(10):1403-12. [Link] [DOI:10.1016/j.freeradbiomed.2008.08.014]
33. Park K, Lee JH. Photosensitizer effect of curcumin on UVB-irradiated HaCaT cells through activation of caspase pathways. Oncol Rep. 2007;17(3):537-40. [Link] [DOI:10.3892/or.17.3.537]
34. Gao X, Deeb D, Jiang H, Liu YB, Dulchavsky SA, Gautam SC. Curcumin differentially sensitizes malignant glioma cells to TRAIL/Apo2L-mediated apoptosis through activation of procaspases and release of cytochrome c from mitochondria. J Exp Ther Oncol. 2005;5(1):39-48. [Link]
35. Karmakar S, Banik NL, Patel SJ, Ray SK. Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic pathways for apoptosis in human glioblastoma T98G cells. Neurosci Lett. 2006;407(1):53-8. [Link] [DOI:10.1016/j.neulet.2006.08.013]
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