Genotoxicity Study of Carboxymethyl Chitosan-based Hydrogel for Clinical Use
Main Article Content
Abstract
A carboxymethyl chitosan-based hydrogel used for hemostatic and anti-adhesive on wounds was assessed by a genotoxicity test.
The hydrogel was assessed for its potential to induce bacterial reverse mutation in the histidine auxotroph strains of Salmonella typhimurium and in the tryptophan auxotroph strain of Escherichia coli WP2uvrA. The study was performed with five bacterial test strains at different concentrations of hydrogel, with a negative control, and with five different types of positive controls, both in the presence and absence of a metabolic activation system. In all test strains used, there was no increase in the number of revertant colonies compared to the negative control at any concentration of test item either in the presence of or in the absence of a metabolic activation system. To evaluate additional genotoxicity of carboxymethyl chitosan hydrogel, the chromosome aberration test was performed using a cultured Chinese hamster lung cell line in the absence and presence of a metabolic activation system.
The results of the bacterial reverse mutation assay indicated no mutagenic response at the concentration range tested, under the conditions of this study. The chromosome aberration test showed no significant increase of chromosome aberration in cells in metaphase arrest compared to the groups treated with vehicle control. Therefore, the carboxymethyl chitosan-based hydrogel is considered not to induce genotoxicity under the test system utilized.
Article Details
How to Cite
LEE, Kwang Il et al.
Genotoxicity Study of Carboxymethyl Chitosan-based Hydrogel for Clinical Use.
Medical Research Archives, [S.l.], v. 10, n. 12, dec. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3436>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v10i12.3436.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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51. Liu X, He Z, Chen Y, et al. Dual drug delivery system of photothermal-sensitive carboxymethyl chitosan nanosphere for photothermal-chemotherapy. Int J Biol Macromol. Nov 15 2020;163:156-166. doi:10.1016/j.ijbiomac.2020.06.202
2. Ho TC, Chang CC, Chan HP, et al. Hydrogels: Properties and Applications in Biomedicine. Molecules. May 2 2022;27(9)doi:10.3390/molecules27092902
3. Zhang L, Liu M, Zhang Y, Pei R. Recent Progress of Highly Adhesive Hydrogels as Wound Dressings. Biomacromolecules. Oct 12 2020;21(10):3966-3983. doi:10.1021/acs.biomac.0c01069
4. Li D, Chen J, Wang X, Zhang M, Li C, Zhou J. Recent Advances on Synthetic and Polysaccharide Adhesives for Biological Hemostatic Applications. Front Bioeng Biotechnol. 2020;8:926. doi:10.3389/fbioe.2020.00926
5. Cao Z, Luo Y, Li Z, et al. Antibacterial Hybrid Hydrogels. Macromol Biosci. Jan 2021;21(1):e2000252. doi:10.1002/mabi.202000252
6. Pourshahrestani S, Zeimaran E, Kadri NA, Mutlu N, Boccaccini AR. Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing. Adv Healthc Mater. Oct 2020;9(20):e2000905. doi:10.1002/adhm.202000905
7. Peers S, Montembault A, Ladavière C. Chitosan hydrogels for sustained drug delivery. J Control Release. Oct 10 2020;326:150-163. doi:10.1016/j.jconrel.2020.06.012
8. Gao D, Zhang Y, Bowers DT, Liu W, Ma M. Functional hydrogels for diabetic wound management. APL Bioeng. Sep 2021;5(3):031503. doi:10.1063/5.0046682
9. Ribeiro CT, Dias FA, Fregonezi GA. Hydrogel dressings for venous leg ulcers. Cochrane Database Syst Rev. Aug 5 2022;8(8):Cd010738. doi:10.1002/14651858.CD010738.pub2
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11. Ebhodaghe SO. A short review on chitosan and gelatin-based hydrogel composite polymers for wound healing. J Biomater Sci Polym Ed. Aug 2022;33(12):1595-1622. doi:10.1080/09205063.2022.2068941
12. Kharaziha M, Baidya A, Annabi N. Rational Design of Immunomodulatory Hydrogels for Chronic Wound Healing. Adv Mater. Oct 2021;33(39):e2100176. doi:10.1002/adma.202100176
13. Paul P, Kolesinska B, Sujka W. Chitosan and Its Derivatives - Biomaterials with Diverse Biological Activity for Manifold Applications. Mini Rev Med Chem. 2019;19(9):737-750. doi:10.2174/1389557519666190112142735
14. Alven S, Aderibigbe BA. Chitosan and Cellulose-Based Hydrogels for Wound Management. Int J Mol Sci. Dec 18 2020;21(24)doi:10.3390/ijms21249656
15. Valentine R, Athanasiadis T, Moratti S, Hanton L, Robinson S, Wormald PJ. The efficacy of a novel chitosan gel on hemostasis and wound healing after endoscopic sinus surgery. Am J Rhinol Allergy. Jan-Feb 2010;24(1):70-5. doi:10.2500/ajra.2010.24.3422
16. Patrulea V, Ostafe V, Borchard G, Jordan O. Chitosan as a starting material for wound healing applications. Eur J Pharm Biopharm. Nov 2015;97(Pt B):417-26. doi:10.1016/j.ejpb.2015.08.004
17. Zhu Y, Zhang Y, Zhou Y. Application Progress of Modified Chitosan and Its Composite Biomaterials for Bone Tissue Engineering. Int J Mol Sci. Jun 12 2022;23(12)doi:10.3390/ijms23126574
18. Wang W, Meng Q, Li Q, et al. Chitosan Derivatives and Their Application in Biomedicine. Int J Mol Sci. Jan 12 2020;21(2)doi:10.3390/ijms21020487
19. Tian B, Hua S, Tian Y, Liu J. Chemical and physical chitosan hydrogels as prospective carriers for drug delivery: a review. J Mater Chem B. Nov 18 2020;8(44):10050-10064. doi:10.1039/d0tb01869d
20. Hao Y, Zhao W, Zhang H, Zheng W, Zhou Q. Carboxymethyl chitosan-based hydrogels containing fibroblast growth factors for triggering diabetic wound healing. Carbohydr Polym. Jul 1 2022;287:119336. doi:10.1016/j.carbpol.2022.119336
21. Chen XG, Wang Z, Liu WS, Park HJ. The effect of carboxymethyl-chitosan on proliferation and collagen secretion of normal and keloid skin fibroblasts. Biomaterials. Dec 2002;23(23):4609-14. doi:10.1016/s0142-9612(02)00207-7
22. Shariatinia Z. Carboxymethyl chitosan: Properties and biomedical applications. Int J Biol Macromol. Dec 2018;120(Pt B):1406-1419. doi:10.1016/j.ijbiomac.2018.09.131
23. Upadhyaya L, Singh J, Agarwal V, Tewari RP. Biomedical applications of carboxymethyl chitosans. Carbohydr Polym. Jan 2 2013;91(1):452-66. doi:10.1016/j.carbpol.2012.07.076
24. Lei M, Huang W, Jin Z, Sun J, Zhang M, Zhao S. Effect of molecular structure and ionization state on aggregation of carboxymethyl chitosan: A molecular dynamics study. Carbohydr Polym. Dec 1 2022;297:119993. doi:10.1016/j.carbpol.2022.119993
25. Khalil AM, Abdel-Monem RA, Darwesh OM, Hashim AI, Nada AA, Rabie ST. Synthesis, Characterization, and Evaluation of Antimicrobial Activities of Chitosan and Carboxymethyl Chitosan Schiff-Base/Silver Nanoparticles. Journal of Chemistry. 2017/03/15 2017;2017:1434320. doi:10.1155/2017/1434320
26. Fonseca-Santos B, Chorilli M. An overview of carboxymethyl derivatives of chitosan: Their use as biomaterials and drug delivery systems. Mater Sci Eng C Mater Biol Appl. Aug 1 2017;77:1349-1362. doi:10.1016/j.msec.2017.03.198
27. Wang D, Zhang N, Meng G, He J, Wu F. The effect of form of carboxymethyl-chitosan dressings on biological properties in wound healing. Colloids Surf B Biointerfaces. Oct 2020;194:111191. doi:10.1016/j.colsurfb.2020.111191
28. Fu D, Han B, Dong W, Yang Z, Lv Y, Liu W. Effects of carboxymethyl chitosan on the blood system of rats. Biochem Biophys Res Commun. Apr 29 2011;408(1):110-4. doi:10.1016/j.bbrc.2011.03.130
29. Chung YJ, An SY, Yeon JY, Shim WS, Mo JH. Effect of a Chitosan Gel on Hemostasis and Prevention of Adhesion After Endoscopic Sinus Surgery. Clin Exp Otorhinolaryngol. Jun 2016;9(2):143-9. doi:10.21053/ceo.2015.00591
30. Bringezu F, Simon S. Salmonella typhimurium TA100 and TA1535 and E. coli WP2 uvrA are highly sensitive to detect the mutagenicity of short Alkyl-N-Nitrosamines in the Bacterial Reverse Mutation Test. Toxicol Rep. 2022;9:250-255. doi:10.1016/j.toxrep.2022.02.005
31. Kumaravel TS, Sathya TN, Balaje R, et al. Genotoxicity evaluation of medical devices: A regulatory perspective. Mutat Res Rev Mutat Res. Jan-Jun 2022;789:108407. doi:10.1016/j.mrrev.2021.108407
32. Gatehouse D. Bacterial mutagenicity assays: test methods. Methods Mol Biol. 2012;817:21-34. doi:10.1007/978-1-61779-421-6_2
33. Abbondandolo A. Chromosome-aberration tests. Food Addit Contam. Apr-Jun 1984;1(2):165-72. doi:10.1080/02652038409385839
34. Chien HF, Chen CP, Chen YC, Chang PH, Tsai T, Chen CT. The use of Chitosan to enhance photodynamic inactivation against Candida albicans and its drug-resistant clinical isolates. Int J Mol Sci. Apr 3 2013;14(4):7445-56. doi:10.3390/ijms14047445
35. Pusateri AE, McCarthy SJ, Gregory KW, et al. Effect of a chitosan-based hemostatic dressing on blood loss and survival in a model of severe venous hemorrhage and hepatic injury in swine. J Trauma. Jan 2003;54(1):177-82. doi:10.1097/00005373-200301000-00023
36. Ylitalo R, Lehtinen S, Wuolijoki E, Ylitalo P, Lehtimäki T. Cholesterol-lowering properties and safety of chitosan. Arzneimittelforschung. 2002;52(1):1-7. doi:10.1055/s-0031-1299848
37. Tokura S, Nishimura S-I, Sakairi N, Nishi N. Biological activities of biodegradable polysaccharide. Macromolecular Symposia. 1996;101(1):389-396. doi:https://doi.org/10.1002/masy.19961010144
38. Yang Z, Han B, Fu D, Liu W. Acute toxicity of high dosage carboxymethyl chitosan and its effect on the blood parameters in rats. J Mater Sci Mater Med. Feb 2012;23(2):457-62. doi:10.1007/s10856-011-4467-4
39. Kalliola S, Repo E, Srivastava V, et al. Carboxymethyl Chitosan and Its Hydrophobically Modified Derivative as pH-Switchable Emulsifiers. Langmuir. Feb 27 2018;34(8):2800-2806. doi:10.1021/acs.langmuir.7b03959
40. Mourya VK, Inamdara N, Ashutosh Tiwari N. Carboxymethyl Chitosan And Its Applications. Advanced Materials Letters. 2010;1(1):11-33. doi:10.5185/amlett.2010.3108
41. Jayakumar R, Nagahama H, Furuike T, Tamura H. Synthesis of phosphorylated chitosan by novel method and its characterization. Int J Biol Macromol. May 1 2008;42(4):335-9. doi:10.1016/j.ijbiomac.2007.12.011
42. Desislava Tzaneva AS, Nadezhda Petkova, Ventzislav Nenov, Albena Stoyanova, Panteley Denev. Synthesis of Carboxymethyl Chitosan and its Rheological Behaviour in Pharmaceutical and Cosmetic Emulsions. vol Volume: 7. ssue: 10; 2017:070-078.
43. Lim JW, Lim JH, Kim CZ, Lee SU, Lee SJ. Intraocular Inflammation after Use of Anti-adhesion Agents. J Retin. 2022;7(1):16-20. doi:10.21561/jor.2022.7.1.16
44. Katugampola P, Winstead C, Adeleke A. Thermal stability of carboxymethyl chitosan varying the degree of substitution. 2014:
45. Souza M, Carvalho Gd, Stamford TCM, Tenório PP, Sampaio FC, Pessoa J. Chitosan as an oral antimicrobial agent. 2011:
46. Müller WE, Neufurth M, Wang S, Tolba E, Schröder HC, Wang X. Morphogenetically active scaffold for osteochondral repair (polyphosphate/alginate/N,O-carboxymethyl chitosan). Eur Cell Mater. Feb 22 2016;31:174-90. doi:10.22203/ecm.v031a12
47. Zhang XY, Chen YP, Han J, et al. Biocompatiable silk fibroin/carboxymethyl chitosan/strontium substituted hydroxyapatite/ cellulose nanocrystal composite scaffolds for bone tissue engineering. Int J Biol Macromol. Sep 1 2019;136:1247-1257. doi:10.1016/j.ijbiomac.2019.06.172
48. Rao KM, Sudhakar K, Suneetha M, Won SY, Han SS. Fungal-derived carboxymethyl chitosan blended with polyvinyl alcohol as membranes for wound dressings. Int J Biol Macromol. Nov 1 2021;190:792-800. doi:10.1016/j.ijbiomac.2021.09.034
49. Shi Y, Xiong Z, Lu X, Yan X, Cai X, Xue W. Novel carboxymethyl chitosan-graphene oxide hybrid particles for drug delivery. J Mater Sci Mater Med. Nov 2016;27(11):169. doi:10.1007/s10856-016-5774-6
50. Yan Y, Wu Q, Ren P, et al. Zinc ions coordinated carboxymethyl chitosan-hyaluronic acid microgel for pulmonary drug delivery. Int J Biol Macromol. Dec 15 2021;193(Pt B):1043-1049. doi:10.1016/j.ijbiomac.2021.11.088
51. Liu X, He Z, Chen Y, et al. Dual drug delivery system of photothermal-sensitive carboxymethyl chitosan nanosphere for photothermal-chemotherapy. Int J Biol Macromol. Nov 15 2020;163:156-166. doi:10.1016/j.ijbiomac.2020.06.202