Comprehensive cytotoxicity analysis of polysaccharide hydrogel modified with cerium oxide nanoparticles for wound healing application
https://doi.org/10.17586/2220-8054-2021-12-3-329-335
Abstract
This paper is aimed at the experimental study (in animal models) of acute toxicity and irritating properties of polysaccharide hydrogel modified with cerium oxide nanoparticles. In the acute experiment, there were no indications of irritating action of the gel at the site of application when the hydrogel was administered intragastrically or epicutaneously. No lethal effects were registered during this experiment even at the highest concentration. The results obtained demonstrate the lack of acute toxicity and local irritability of the synthesized hybrid hydrogel, which allows to classify the developed hybrid hydrogel as the relatively low-risk drug.
Keywords
wound healing,
hydrogel,
cerium oxide nanoparticles,
epicutaneous application,
regeneration,
cell proliferation
Supporting agencies: The reported study was funded by the grant of the President of the Russian Federation MK-138.2020.3. Synthesis of CeO2-containing hydrogels was performed by K. Kamenskikh with the support from RFBR grant 19-34-90031.
About the Authors
A. L. Popov
Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences; Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences
Russian Federation
Russian Federation
A. L. Popov
Institutskaya str., 3, Pushchino, 142290
Leninskiy prosp., 31, Moscow, 119991
V. V. Andreeva
Moscow Regional Research and Clinical Institute, Laboratory of Medical and Physics Research
Russian Federation
Russian Federation
V.V. Andreeva
Shchepkina str. 61/2, Moscow, 129110
N. V. Khohlov
I. M. Sechenov First Moscow State Medical University
Russian Federation
Russian Federation
N.V. Khohlov
Bolshaya Pirogovskaya str., 19s1, Moscow, 119146
K. A. Kamenskikh
Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences
Russian Federation
Russian Federation
K.A. Kamenskikh
Institutskaya str., 3, Pushchino, 142290
V. B. Gavrilyuk
Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences
Russian Federation
Russian Federation
V.B. Gavrilyuk
Institutskaya str., 3, Pushchino, 142290
V. K. Ivanov
Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences
Russian Federation
Russian Federation
V.K. Ivanov
Leninskiy prosp., 31, Moscow, 119991
References
1. Bellio P., Luzi C., Mancini A., Cracchiolo S., Passacantando M., Di Pietro L., Perilli M., Amicosante G., Santucci S., Celenza G. Cerium oxide nanoparticles as potential antibiotic adjuvant. Effects of CeO2 nanoparticles on bacterial outer membrane permeability. Biochim. Biophys. Acta Biomembr., 2018, 1860, P. 2428–2435.
2. Popov A., Popova, N., Gould D., Shcherbakov A., Sukhorukov G., Ivanov V. Ceria nanoparticles-decorated microcapsules as a smart drug delivery/protective system: Protection of encapsulated P. pyralis luciferase. ACS Appl. Mater. Interfaces, 2018, 10(17), P. 14367–14377.
3. Rocca A., Mattoli V., Mazzolai B., Ciofani G. Cerium Oxide Nanoparticles Inhibit Adipogenesis in Rat Mesenchymal Stem Cells: Potential Therapeutic Implications. Pharm. Res., 2014, 31, P. 2952–2962.
4. Sridharan P., Vinothkumar G., Pratheesh P., Suresh Babu K. Biomimetic potential of cerium oxide nanoparticles in modulating the metabolic gene signature in GBM-derived cell lines. J Mater Sci., 2020, 55, P. 11622–11636.
5. Zhou D., Fang T., Lu L.-Q., Yi L. Neuroprotective potential of cerium oxide nanoparticles for focal cerebral ischemic stroke. J. Huazhong Univ. Sci. Technol., 2016, 36, P. 480–486.
6. Hirst S.M., Karakoti A.S., Tyler R.D., Sriranganathan N., Seal S., Reilly C.M. Anti-inflammatory properties of cerium oxide nanoparticles. Small, 2009, 5(24), P. 2848–2856.
7. Celardo I., Pedersen J.Z., Traversa E., Ghibelli L. Pharmacological potential of cerium oxide nanoparticles. Nanoscale, 2011, 3(4), P. 1411–1420.
8. Malyukin Y., Maksimchuk P., Seminko V., Okrushko E., Spivak N. Limitations of Self-Regenerative Antioxidant Ability of Nanoceria Imposed by Oxygen Diffusion. J. Phys. Chem. C, 2018, 122(28), P. 16406–16411.
9. Seminko V., Maksimchuk P., Grygorova G., Malyukin Y.V. Mechanism and Dynamics of Fast Redox Cycling in Cerium Oxide Nanoparticles at High Oxidant Concentration. J. Phys. Chem. C, 2021, 125(8), P. 4743–4749.
10. Seminko V., Maksimchuk P., Grygorova G., Avrunin O., Semenets V., Klochkov V., Malyukin Y. Catalytic Decomposition of Hypochlorite Anions by Ceria Nanoparticles Visualized by Spectroscopic Techniques. J. Phys. Chem. C, 2019, 123(33), P. 20675–20681.
11. Klochkov V.K., Sedyh O.O., Grygorova G.V., Viagin O.G., Opolonin A.D., Malyukin Yu.V. Induction and inhibition of free radicals by the GdVO4:Eu3+ and CeO2 nanoparticles under X-ray irradiation. Funct. Mater., 2018, 25(2), P. 294–299.
12. Klochkov V.K., Malyukin Yu.V., Grygorova G.V., Sedyh O.O., Kavok N.S., Seminko V.V., Semynozhenko V.P. Oxidation-reduction processes in CeO2-x nanocrystals under UV irradiation. J. Photochem. Photobiol. A, 2018, 364, P. 282–287.
13. Malyukin Y., Klochkov V., Maksimchuk P., Seminko V., Spivak N. Oscillations of cerium oxidation state driven by oxygen diffusion in colloidal nanoceria (CeO2-x). Nanoscale Res. Lett., 2017, 12(1), P. 566.
14. Alpaslan E., Yazici H., Golshan N.H., Ziemer K.S., Webster T.J. pH-Dependent Activity of Dextran-Coated Cerium Oxide Nanoparticles on Prohibiting Osteosarcoma Cell Proliferation. ACS Biomater. Sci. Eng., 2015, 1(11), P. 1096–1103.
15. Ivanov V.K., Shcherbakov A.B., Usatenko A.V. Structure-sensitive properties and biomedical applications of nanodispersed cerium dioxide. Russ. Chem. Rev., 2009, 78(9), P. 855–871.
16. Lord M.S., Jung M., Teoh W.Y., Gunawan C., Vassie J.A., Amal R., Whitelock J.M. Cellular uptake and reactive oxygen species modulation of cerium oxide nanoparticles in human monocyte cell line U937. Biomaterials, 2012, 33(31), P. 7915–7924.
17. Ciofani G., Genchi G.G., Liakos I., Cappello V., Gemmi M., Athanassiou A., Mazzolai B., Mattoli V. Effects of cerium oxide nanoparticles on PC12 neuronal-like cells: Proliferation, differentiation, and dopamine secretion. Pharm Res., 2013, 30, P. 2133–2145.
18. Niu J., Azfer A., Rogers L.M.,Wang X., Kolattukudy P.E. Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc. Res., 2007, 73, P. 549–559.
19. Chen S., Hou Y., Cheng G., Zhang C., Wang S., Zhang J. Cerium oxide nanoparticles protect endothelial cells from apoptosis induced by oxidative stress. Biol. Trace Elem. Res., 2013, 154, P. 156–166.
20. Lu B., Zhu D.-Y., Yin J.-H., Xu H., Zhang C.-Q., Ke Q.-F., Gao Y.-S., Guo Y.-P. Incorporation of cerium oxide in hollow mesoporous bioglass scaffolds for enhanced bone regeneration by activating the ERK signaling pathway. Biofabrication, 2019, 11(2), P. 025012.
21. Alpaslan E., Geilich B.M., Yazici H., Webster T.J. pH-Controlled Cerium Oxide Nanoparticle Inhibition of Both Gram-Positive and Gram- Negative Bacteria Growth. Sci. Rep., 2017, 7, P. 45859.
22. Agarwal C., Aggrawal S., Dutt D., Mohanty P. Cerium oxide immobilized paper matrices for bactericidal application. Mater. Sci. Eng. B, 2018, 232–235, P. 1–7.
23. Mohamed H.E.A., Afridi S., Khalil A.T., Ali M., Zohra T., Akhtar R., Ikram A., Shinwari Z.K., Maaza M. Promising antiviral, antimicrobial and therapeutic properties of green nanoceria. Nanomedicine, 2020, 15(5), P. 467–488.
24. Popov A.L., Popova N.R., Selezneva I.I., Akkizov A.Y., Ivanov V.K. Cerium oxide nanoparticles stimulate proliferation of primary mouse embryonic fibroblasts in vitro. Mater. Sci. Eng. C, 2016, 68, P. 406–413.
25. Thoniyot P., Tan M.J., Karim A.A., Young D.J., Loh X.J. Nanoparticle–Hydrogel Composites: Concept, Design, and Applications of These Promising, Multi Functional Materials. Adv. Sci., 2015, 2, P. 1400010.
26. Dannert C., Stokke B.T., Dias R.S. Nanoparticle-Hydrogel Composites: From Molecular Interactions to Macroscopic Behavior. Polymers, 2019, 11(2), P. 275.
27. Almjasheva O.V., Garabadzhiu A.V., Kozina Yu.V., Litvinchuk L.F., Dobritsa V.P. Biological effect of zirconium dioxide-based nanoparticles. Nanosyst. Phys. Chem. Math., 2017, 8(3), P. 391–396.
28. Gosselin R.E., Hodge H., Smith R.P., Gleason M.N. Clinical Toxicology of Commercial Products: Acute Poisoning. Williams and Wilkins, Baltimore, 1976, 332 p.
29. Popova N.R., Andreeva V.V., Khohlov N.V., Popov A.L., Ivanov V.K. Fabrication of CeO2 nanoparticles embedded in polysaccharide hydrogel and their application in skin wound healing. Nanosyst. Phys. Chem. Math., 2020, 11(1), P. 99–109.
Review
For citations:
Popov A.L., Andreeva V.V., Khohlov N.V., Kamenskikh K.A., Gavrilyuk V.B., Ivanov V.K. Comprehensive cytotoxicity analysis of polysaccharide hydrogel modified with cerium oxide nanoparticles for wound healing application. Nanosystems: Physics, Chemistry, Mathematics. 2021;12(3):329-335. https://doi.org/10.17586/2220-8054-2021-12-3-329-335
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