Tuba TARHAN

Synthesis and characterization of magnetic nanocomposite for in vitro evaluation of irinotecan using human cell lines

In this study, magnetic O-carboxymethyl chitosan (MOCC) nanocomposite was synthesized and characterized as a drug delivery system for loading the anticancer drug irinotecan (CPT-11). To increase the drug loading capacity, MOCC was synthesized by linking the carboxyl group functionally to chitosan. Also, several critical factors such as concentration, the dose of MOCC, and contact time for optimum drug loading condition were investigated. The loading capacity of CPT-11 onto MOCC was calculated as 5.6 mg/g, and the loaded drug concentration was calculated as 0.04787 mM at pH value of 5. Besides, the cytotoxic properties of MOCC, CPT11 loaded MOCC (MOCC-CPT-11), and free CPT-11 were studied on glioblastoma multiforme cell lines, including U87 and U373. According to the results, the MOCC-CPT-11 showed at least as toxic effect as free CPT-11 even at very low concentrations, while the MOCC showed slight toxicity (cell viability of 96% to 78%) on U373 cell lines at all concentrations and for 24 h and 48 h incubation times. Moreover, the results showed that the MOCC indicated significant toxicity in increasing concentrations and incubation times, and the MOCC-CPT-11 is as toxic as free CPT-11 on U87 cells at all concentrations and incubation times.

PDF

___

1. Vredenburgh JJ, Desjardins A, Reardon DA, Friedman HS. Experience with irinotecan for the treatment of malignant glioma. Neuro Oncology 2009; 11 (1): 80-91. doi: 10.1215/15228517-2008-075
2. Tarhan T, Tural B, Tural S. Synthesis and characterization of new branched magnetic nanocomposite for loading and release of topotecan anticancer drug. Journal of Analytical Science and Technology 2019; 10: 30. doi: 10.1186/s40543-019-0189-x
3. Cao Q, Han X, Li L. Enhancement of the efficiency of magnetic targeting for drug delivery: development and evaluation of magnet system. Journal of Magnetism and Magnetic Materials 2011; 323 (15): 1919-1924. doi: 10.1016/j.jmmm.2010.11.058
4. Huang JR, Lee MH, Li WS, Wu HC. Liposomal irinotecan for treatment of colorectal cancer in a preclinical model. Cancers 2019; 11: 281. doi:10.3390/cancers11030281
5. Casadó A, Mora M, Sagristá ML, Varona SR, Acedo P et al. Improved selectivity and cytotoxic effects of irinotecan via liposomal delivery: a comparative study on Hs68 and HeLa cells. European Journal of Pharmaceutical Sciences 2017; 109: 65-77. doi: 10.1016/j.ejps.2017.07.024
6. Gao F, Yuan Q, Gao L, Cai P, Zhu H et al. Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles. Biomaterials 2014; 35 (33): 8854-8866. doi: 10.1016/j.biomaterials.2014.07.004
7. Mai TTT, Ha PT, Pham HN, Le TTH, Pham HL et al. Chitosan and O-carboxymethyl chitosan modified $Fe_3O_4$ for hyperthermic treatment. Advances in Natural Sciences: Nanoscience and Nanotechnology 2012; 3. doi:10.1088/2043-6262/3/1/015006
8. Zhu A, Yuan L, Jin W, Dai S, Wang Q et al. Polysaccharide surface modified $Fe_3O_4$ nanoparticles for camptothecin loading and release. Acta Biomaterialia 2009; 5 (5): 1489-1498. doi: 10.1016/j.actbio.2008.10.022
9. Li G, Huang K, Jiang Y, Ding P, Yang D. Preparation and characterization of carboxyl functionalization of chitosan derivative magnetic nanoparticles. Biochemical Engineering Journal 2008; 40 (3): 408-414. doi: 10.1016/j.bej.2008.01.018
10. Qu J, Liu G, Wang Y, Hong R. Preparation of $Fe_3O_4$ –chitosan nanoparticles used for hyperthermia. Advanced Powder Technology 2010; 21 (4): 461-467. doi: 10.1016/j.apt.2010.01.008
11. Chen S, Zhong H, Zhang L, Wang Y, Cheng Z et al. Synthesis and characterization of thermoresponsive and biocompatible core–shell microgels based on N-isopropylacrylamide and carboxymethyl chitosan. Carbohydrate Polymers 2010; 82 (3): 747-752. doi: 10.1016/j. carbpol.2010.05.046
12. Vangijzegem T, Stanicki D, Laurent S. Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics. Expert Opinion on Drug Delivery 2019; 16 (1): 69-78. doi: 10.1080/17425247.2019.1554647.2
13. Wen Y, Wang Y, Liu X, Zhang W, Xiong X et al. Camptothecin-based nanodrug delivery systems. Cancer Biology & Medicine 2017; 14 (4): 363-370. doi: 10.20892/j.issn.2095-3941.2017.0099
14. Allen C, Maysinger D, Eisenberg A. Nano-engineering block copolymer aggregates for drug delivery. Colloids and Surfaces B: Biointerfaces 1999; 16: 3-27. doi: 10.1016/S0927-7765(99)00058-2
15. Mohammadi-Samani S, Miri R, Salmanpour M, Khalighian N, Sotoudeh S et al. Preparation and assessment of chitosan-coated superparamagnetic $Fe_3O_4$ nanoparticles for controlled delivery of methotrexate. Research in Pharmaceutical Sciences 2013; 8 (1): 25-33.
16. Mourya VK, Inamdar NN, Tiwari A. Carboxymethyl chitosan and its applications. Advanced Materials Letters 2010; 1 (1): 11-33. doi: 10.5185/amlett.2010.3108
17. Safee NHA, Abdullah MP, Othman MR. Carboxymethyl chitosan-$Fe_3O_4$ nanoparticles: synthesis and characterization. Malaysian Journal of Analytical Sciences 2010; 14 (2): 63-68.
18. Taylor RR, Tang Y, Gonzalez MV, Stratford PW, Lewis AL. Irinotecan drug eluting beads for use in chemoembolization: in vitro and in vivo evaluation of drug release properties. European Journal of Pharmaceutical Sciences 2007; 30: 7-14. doi: 10.1016/j.ejps.2006.09.002
19. Jiang DS, Long SY, Huang J, Xiao HY, Zhou JY. Immobilization of Pycnoporus sanguineus laccase on magnetic chitosan microspheres. Biochemical Engineering Journal 2005; 25 (1): 15-23. doi: 10.1016/j.bej.2005.03.007
20. Kamari A, Ngah WW, Chong M, Cheah M. Sorption of acid dyes onto GLA and $H_2SO_4$ cross-linked chitosan beads. Desalination 2009; 249 (3): 1180-1189. doi: 10.1016/j.desal.2009.04.010
21. Zhang J, Xu Z, Chen H, Zong Y. Removal of 2,4-dichlorophenol by chitosan-immobilized laccase from Coriolus versicolor. Biochemical Engineering Journal 2009; 45 (1): 54-59. doi: 10.1016/j.bej.2009.02.005
22. Fan C, Gao W, Chen Z, Fan H, Li M et al. Tumor selectivity of stealth multi-functionalized superparamagnetic iron oxide nanoparticles. International Journal of Pharmaceutics 2011; 404 (1): 180-190. doi: 10.1016/j.ijpharm.2010.10.038
23. Chen X, Lv H, Ye M, Wang S, Ni E et al. Novel superparamagnetic iron oxide nanoparticles for tumor embolization application: preparation, characterization and double targeting. International Journal of Pharmaceutics 2012; 426 (1): 248-255. doi: 10.1016/j.ijpharm.2012.01.043
24. Aziz T, Masum SM, Qadir MR. Gafur A, Huq D. Physicochemical characterization of iron oxide nanoparticle coated with chitosan for biomedical application. International Research Journal of Pure and Applied Chemistry 2016; 11 (1): 1-9. doi: 10.9734/IRJPAC/2016/23408
25. Babu PC, Sundaraganesan N, Sudha S, Aroulmoji V, Murano E. Molecular structure and vibrational spectra of Irinotecan: a density functional theoretical study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2012; 98: 1-6. doi: 10.1016/j. saa.2012.08.005
26. Wang C, Luo H, Zhang Z, Wu Y, Zhang J et al. Removal of As (III) and As (V) from aqueous solutions using nanoscale zero valent ironreduced graphite oxide modified composites. Journal of Hazardous Materials 2014; 268: 124-131. doi: 10.1016/j.jhazmat.2014.01.009
27. Zhang K, Zheng H, Liang S, Gao C. Aligned PLLA nanofibrous scaffolds coated with graphene oxide for promoting neural cell growth. Acta Biomaterialia 2016; 37: 131-142. doi: 10.1016/j.actbio.2016.04.008
28. Chellouli M, Chebabe D, Dermaj A, Erramli H, Bettach N et al. Corrosion inhibition of iron in acidic solution by a green formulation derived from Nigella sativa L. Electrochimica Acta 2016; 204: 50-59. doi: 10.1016/j.electacta.2016.04.015
29. Zheng X, Huang T, Pan Y, Wang W, Fang G et al. 3,3′-sulfonyldipropionitrile: a novel electrolyte additive that can augment the high-voltage performance of $LiNi_{1/3}Co_{1/3}Mn_{1/3}O|2$ /graphite batteries. Journal of Power Sources 2016; 319: 116-123. doi: 10.1016/j.jpowsour.2016.04.053
30. Anderson J, Kuhn M, Diebold U. Epitaxially grown $Fe_3O_4$ thin films: an XPS study. Surface Science Spectra 1996; 4 (3): 266-272. doi: 10.1116/1.1247796
31. Unsoy G, Yalcin S, Khodadust R, Gunduz G, Gunduz U. Synthesis optimization and characterization of chitosan-coated iron oxide nanoparticles produced for biomedical applications. Journal of Nanoparticle Research 2012; 14 (11): 964. doi: 10.1007/s11051-012-0964-8
32. Xing Y, Jin YY, Si JC, Peng ML, Wang XF et al. Controllable synthesis and characterization of $Fe_3O_4$ /Au composite nanoparticles. Journalof Magnetism and Magnetic Materials 2015; 380: 150-156. doi: 10.1016/j.jmmm.2014.09.060