Abstract
Amino-functionalized mesoporous silica (MS-NH2) was synthesized, characterized, and applied as an adsorbent and antidote agent of methotrexate (MTX) in vitro and in vivo assessment. Different techniques, such as FT-IR and XRD, analyzed the structure. The texture parameters were determined by the N2 adsorption/desorption technique. The morphology was examined using FE-SEM. Prepared materials showed to have high porosity and nano-sized pores. The capacity of synthesized material in the adsorption of MTX was checked. The in vivo experiments were performed on mice that were overdosed with MTX. Serum biomarkers were assessed, and it was discovered that MS-NH2 administration effectively decreased MTX toxicity. Furthermore, in vivo evaluation was conducted for the long-term administration of MS-NH2 in the animal model. Analysis of plasma biomarkers showed no significant changes in organ injury after long-term administration. Cytotoxicity and LDH assay showed that MS-NH2 did not impose toxicity and damage in the studied cell line.
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References
G.D. Weinstein, G.M. White, An approach to the treatment of moderate to severe psoriasis with rotational therapy. J. Am. Acad. Dermatol. 28(3), 454–459 (1993)
B.N. Cronstein, J.R. Bertino, Methotrexate (Springer Science and Business Media, Berlin, 2000)
W. Wang, H. Zhou, L. Liu, Side effects of methotrexate therapy for rheumatoid arthritis: a systematic review. Eur. J. Med. Chem. (2018). https://doi.org/10.1016/j.ejmech.2018.09.027
M. Aghajanzadeh, M. Zamani, H. Molavi, H. Khieri Manjili, H. Danafar, A. Shojaei, Preparation of metal-organic frameworks UiO-66 for adsorptive removal of methotrexate from aqueous solution. J. Inorg. Organomet. Polym Mater. 28(1), 177–186 (2018). https://doi.org/10.1007/s10904-017-0709-3
F. Farjadian, P. Ahmadpour, S.M. Samani, M. Hosseini, Controlled size synthesis and application of nanosphere MCM-41 as potent adsorber of drugs: a novel approach to new antidote agent for intoxication. Microporous Mesoporous Mater. 213, 30–39 (2015)
G. Choi, T.-H. Kim, J.-M. Oh, J.-H. Choy, Emerging nanomaterials with advanced drug delivery functions; focused on methotrexate delivery. Coord. Chem. Rev. 359, 32–51 (2018). https://doi.org/10.1016/j.ccr.2018.01.007
M. Ghorbani, F. Mahmoodzadeh, B. Jannat, N.F. Maroufi, B. Hashemi, L. Roshangar, Glutathione and pH-responsive fluorescent nanogels for cell imaging and targeted methotrexate delivery. Polym. Adv. Technol. 30(7), 1847–1855 (2019). https://doi.org/10.1002/pat.4617
F. Hao, R.J. Lee, C. Yang, L. Zhong, Y. Sun, S. Dong, Z. Cheng, L. Teng, Q. Meng, J. Lu, Targeted co-delivery of siRNA and methotrexate for tumor therapy via mixed micelles. Pharmaceutics 11(2), 92 (2019)
J. Chen, L. Huang, H. Lai, C. Lu, M. Fang, Q. Zhang, X. Luo, Methotrexate-loaded PEGylated chitosan nanoparticles: synthesis, characterization, and in vitro and in vivo antitumoral activity. Mol. Pharm. 11(7), 2213–2223 (2013)
F. Farjadian, S. Ghasemi, S. Mohammadi-Samani, Hydroxyl-modified magnetite nanoparticles as novel carrier for delivery of methotrexate. Int. J. Pharm. 504(1–2), 110–116 (2016)
Q. Gao, J. Xu, X.-H. Bu, Recent advances about metal–organic frameworks in the removal of pollutants from wastewater. Coord. Chem. Rev. 378, 17–31 (2019). https://doi.org/10.1016/j.ccr.2018.03.015
A.A. Basheer, New generation nano-adsorbents for the removal of emerging contaminants in water. J. Mol. Liq. 261, 583–593 (2018). https://doi.org/10.1016/j.molliq.2018.04.021
F. Farjadian, A. Ghasemi, O. Gohari, A. Roointan, M. Karimi, M.R. Hamblin, Nanopharmaceuticals and nanomedicines currently on the market: challenges and opportunities. Nanomedicine 14(1), 93–126 (2018)
F. Farjadian, A. Roointan, S. Mohammadi-Samani, M. Hosseini, Mesoporous silica nanoparticles: synthesis, pharmaceutical applications, biodistribution, and biosafety assessment. Chem. Eng. J. 359, 684–705 (2019). https://doi.org/10.1016/j.cej.2018.11.156
A.M. Abdelsamad, A.S. Khalil, M. Ulbricht, Influence of controlled functionalization of mesoporous silica nanoparticles as tailored fillers for thin-film nanocomposite membranes on desalination performance. J. Membr. Sci. 563, 149–161 (2018)
F. Farjadian, S. Azadi, S. Mohammadi-Samani, H. Ashrafi, A. Azadi, A novel approach to the application of hexagonal mesoporous silica in solid-phase extraction of drugs. Heliyon 4(11), e00930 (2018). https://doi.org/10.1016/j.heliyon.2018.e00930
M. Mathelié-Guinlet, I. Gammoudi, L. Beven, F. Moroté, M.-H. Delville, C. Grauby-Heywang, T. Cohen-Bouhacina, Silica nanoparticles assisted electrochemical biosensor for the detection and degradation of Escherichia Coli bacteria. Procedia Eng. 168, 1048–1051 (2016). https://doi.org/10.1016/j.proeng.2016.11.337
F.W. Pratiwi, C.W. Kuo, S.-H. Wu, Y.-P. Chen, C.Y. Mou, P. Chen, Chapter Six - The bioimaging applications of mesoporous silica nanoparticles, in The Enzymes, vol. 43, ed. by F. Tamanoi (Academic Press, Cambridge, 2018), pp.123–153
F. Farjadian, M. Hosseini, S. Ghasemi, B. Tamami, Phosphinite-functionalized silica and hexagonal mesoporous silica containing palladium nanoparticles in Heck coupling reaction: synthesis, characterization, and catalytic activity. RSC Adv. 5(97), 79976–79987 (2015)
M. Vallet-Regí, M. Colilla, I. Izquierdo-Barba, M. Manzano, Mesoporous silica nanoparticles for drug delivery: current insights. Molecules (Basel, Switzerland) 23(1), 47 (2017). https://doi.org/10.3390/molecules23010047
F. Farjadian, M. Moghadam, M. Monfared, S. Mohammadi-Samani, Mesoporous silica nanostructure modified with azo gatekeepers for colon targeted delivery of 5-fluorouracil. AIChE J. 68, e17900 (2022)
K. Zarkesh, R. Heidari, P. Iranpour, N. Azarpira, F. Ahmadi, S. Mohammadi-Samani, F. Farjadian, Theranostic hyaluronan coated EDTA modified magnetic mesoporous silica nanoparticles for targeted delivery of cisplatin. J. Drug Deliver.Sci. Technol. 77, 103903 (2022)
M. Akbarian, M. Gholinejad, S. Mohammadi-Samani, F. Farjadian, Theranostic mesoporous silica nanoparticles made of multi-nuclear gold or carbon quantum dots particles serving as pH responsive drug delivery system. Microporous Mesoporous Mater. 329, 111512 (2022)
M. Akbarian, L. Tayebi, S. Mohammadi-Samani, F. Farjadian, Mechanistic assessment of functionalized mesoporous silica-mediated insulin fibrillation. J. Phys. Chem. B 124(9), 1637–1652 (2020)
C. Bharti, U. Nagaich, A.K. Pal, N. Gulati, Mesoporous silica nanoparticles in target drug delivery system: A review. Int. J. Pharm. Invest. 5(3), 124 (2015)
S.B. Hartono, N.T. Phuoc, M. Yu, Z. Jia, M.J. Monteiro, S. Qiao, C. Yu, Functionalized large pore mesoporous silica nanoparticles for gene delivery featuring controlled release and co-delivery. J. Mater. Chem. B 2(6), 718–726 (2014). https://doi.org/10.1039/c3tb21015d
S. Fritsch-Decker, Z. An, J. Yan, I. Hansjosten, M. Al-Rawi, R. Peravali, S. Diabaté, C. Weiss, Silica nanoparticles provoke cell death independent of p53 and BAX in human colon cancer cells. Nanomaterials 9(8), 1172 (2019)
F. Farjadian, S. Ghasemi, R. Heidari, S. Mohammadi-Samani, In vitro and in vivo assessment of EDTA-modified silica nano-spheres with supreme capacity of iron capture as a novel antidote agent. Nanomed. Nanotechnol. Biol. Med. 13(2), 745–753 (2017). https://doi.org/10.1016/j.nano.2016.10.012
E.R. Taqanaki, R. Heidari, M. Monfared, L. Tayebi, A. Azadi, F. Farjadian, EDTA-modified mesoporous silica as supra adsorbent of copper ions with novel approach as an antidote agent in copper toxicity. Int. J. Nanomed. 14, 7781 (2019)
H. Mohammadi, R. Heidari, S.V. Niknezhad, A. Jamshidzadeh, F. Farjadian, In vitro and in vivo evaluation of succinic acid-substituted mesoporous silica for ammonia adsorption: potential application in the management of hepatic encephalopathy. Int. J. Nanomed. 15, 10085 (2020)
S. Radi, S. Tighadouini, M. El Massaoudi, T.B. Hadda, M. Zaghrioui, M. Bacquet, J.P. Dacquin, I. Warad, Synthesis of 1-(Pyrrol-2-yl) imine modified silica as a new sorbent for the removal of toxic metals from aqueous solutions. J. Mater. Environ. Sci. 5, 1280–1287 (2014)
J.G. Croissant, D. Zhang, S. Alsaiari, J. Lu, L. Deng, F. Tamanoi, A.M. AlMalik, J.I. Zink, N.M. Khashab, Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging. J. Control. Release 229, 183–191 (2016)
L. Vaisman, G. Marom, H.D. Wagner, Dispersions of surface-modified carbon nanotubes in water-soluble and water-insoluble polymers. Adv. Func. Mater. 16(3), 357–363 (2006). https://doi.org/10.1002/adfm.200500142
S.K. Nandwani, M. Chakraborty, S. Gupta, Adsorption of surface active ionic liquids on different rock types under high salinity conditions. Sci. Rep. 9(1), 14760 (2019). https://doi.org/10.1038/s41598-019-51318-2
S.K. Lakkaboyana, S. Khantong, N.K. Asmel, A. Yuzir, W.Z. Wan Yaacob, Synthesis of copper oxide nanowires-activated carbon (AC@CuO-NWs) and applied for removal methylene blue from aqueous solution: kinetics, isotherms, and thermodynamics. J. Inorg. Organomet. Polym. Mater. 29(5), 1658–1668 (2019). https://doi.org/10.1007/s10904-019-01128-w
T.F. Parangi, R.M. Patel, U.V. Chudasama, Synthesis and characterization of mesoporous Si-MCM-41 materials and their application as solid acid catalysts in some esterification reactions. Bull. Mater. Sci. 37(3), 609–615 (2014). https://doi.org/10.1007/s12034-014-0709-7
E. Bulut, M. Özacar, İA. Şengil, Adsorption of malachite green onto bentonite: equilibrium and kinetic studies and process design. Microporous Mesoporous Mater. 115(3), 234–246 (2008). https://doi.org/10.1016/j.micromeso.2008.01.039
F. Farjadian, S. Schwark, M. Ulbricht, Novel functionalization of porous polypropylene microfiltration membranes: via grafted poly (Aminoethyl Methacrylate) anchored schiff base toward membrane adsorbers for metal ions. Polyn. Chem. (2014). https://doi.org/10.1039/C4PY01521E
S.J. Allen, G. McKay, J.F. Porter, Adsorption isotherm models for basic dye adsorption by peat in single and binary component systems. J. Colloid Interface Sci. 280(2), 322–333 (2004). https://doi.org/10.1016/j.jcis.2004.08.078
M. Jaroniec, Adsorption on heterogeneous surfaces: The exponential equation for the overall adsorption isotherm. Surf. Sci. 50(2), 553–564 (1975). https://doi.org/10.1016/0039-6028(75)90044-8
A. Ahmadzadeh, N. Zamani, H. Hassanian-Moghaddam, S.K. Hadeiy, P. Parhizgar, Acute versus chronic methotrexate poisoning; a cross-sectional study. BMC Pharmacol. Toxicol. 20(1), 39 (2019). https://doi.org/10.1186/s40360-019-0316-8
J. Florek, R. Caillard, F. Kleitz, Evaluation of mesoporous silica nanoparticles for oral drug delivery–current status and perspective of MSNs drug carriers. Nanoscale 9(40), 15252–15277 (2017)
Y. Yu, Z. Wang, R. Wang, J. Jin, Y.Z. Zhu, Short-term oral administration of mesoporous silica nanoparticles potentially induced colon inflammation in rats through alteration of gut microbiota. Int. J. Nanomed. 16, 881 (2021)
T. Yu, D. Hubbard, A. Ray, H. Ghandehari, In vivo biodistribution and pharmacokinetics of silica nanoparticles as a function of geometry, porosity and surface characteristics. J. Control. Release 163(1), 46–54 (2012)
W.-T. Chan, C.-C. Liu, J.-S.C. Chiau, S.-T. Tsai, C.-K. Liang, M.-L. Cheng, H.-C. Lee, C.-Y. Yeung, S.-Y. Hou, In vivo toxicologic study of larger silica nanoparticles in mice. Int. J. Nanomed. 12, 3421 (2017)
S.P.H. Moghaddam, R. Mohammadpour, H. Ghandehari, In vitro and in vivo evaluation of degradation, toxicity, biodistribution, and clearance of silica nanoparticles as a function of size, porosity, density, and composition. J. Control. Release 311, 1–15 (2019)
R. Mohammadpour, D.L. Cheney, J.W. Grunberger, M. Yazdimamaghani, J. Jedrzkiewicz, K.J. Isaacson, M.A. Dobrovolskaia, H. Ghandehari, One-year chronic toxicity evaluation of single dose intravenously administered silica nanoparticles in mice and their Ex vivo human hemocompatibility. J. Control. Release 324, 471–481 (2020). https://doi.org/10.1016/j.jconrel.2020.05.027
M. Etienne, B. Lebeau, A. Walcarius, Organically-modified mesoporous silica spheres with MCM-41 architecture. New J. Chem. 26(4), 384–386 (2002)
Q. Li, Q.-Y. Yue, Y. Su, B.-Y. Gao, H.-J. Sun, Equilibrium, thermodynamics and process design to minimize adsorbent amount for the adsorption of acid dyes onto cationic polymer-loaded bentonite. Chem. Eng. J. 158(3), 489–497 (2010). https://doi.org/10.1016/j.cej.2010.01.033
R. Heidari, A. Ahmadi, H. Mohammadi, M.M. Ommati, N. Azarpira, H. Niknahad, Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance. Biomed. pharmacother. Biomed. pharmacother. 107, 834–840 (2018). https://doi.org/10.1016/j.biopha.2018.08.050
R. Heidari, S. Behnamrad, Z. Khodami, M.M. Ommati, N. Azarpira, A. Vazin, The nephroprotective properties of taurine in colistin-treated mice is mediated through the regulation of mitochondrial function and mitigation of oxidative stress. Biomed. pharmacother. Biomed. pharmacother. 109, 103–111 (2019). https://doi.org/10.1016/j.biopha.2018.10.093
R. Heidari, V. Taheri, H.R. Rahimi, B. Shirazi Yeganeh, H. Niknahad, A. Najibi, Sulfasalazine-induced renal injury in rats and the protective role of thiol-reductants. Ren. Fail. 38(1), 137–141 (2016). https://doi.org/10.3109/0886022X.2015.1096731
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The funding of this project (95-01-36-13763) was supported by the Research Council of Shiraz University of Medical Sciences.
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FF and RH participated in the conceptualization, ZS and RH participated in the data acquisition, FF, ZS, and NA participated in the data analysis, SM-S, LT, and MD were consultants & performed data analysis. All authors contributed in writing of the manuscript.
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Heidari, R., Sepahi, Z., Mohammadi-Samani, S. et al. Mesoporous silica application as an antidote of methotrexate and evaluation of the long-term oral administration: In vitro and in vivo study. Journal of Materials Research 38, 2930–2942 (2023). https://doi.org/10.1557/s43578-023-01003-y
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DOI: https://doi.org/10.1557/s43578-023-01003-y