Acute Toxicity of Hydrogel Polyhexamethylene Guanidine Hydrochloride

Background. Previously, we have shown that the polyhexamethylene guanidine hydrochloride hydrogel exhibits a pronounced wound healing. At the same time, no studies of the toxic effect of the hydrogel on animals have been conducted.
Aim of the research. In the framework of this work, the acute toxicity of the hydrogel polyhexamethylene guanidine hydrochloride was studied in laboratory animals with intragastric administration.
Materials and methods. The polyhexamethylene guanidine hydrochloride hydrogel was obtained by crosslinking the amino end groups with formaldehyde. An acute toxicity study was carried out (P 1.2.3156-13, GOST 32644-2014 and the Guidelines for conducting preclinical studies of drugs) in an experiment on outbred mice with a single addition of the test substance in different doses (1000, 3000, 5000, 8000 mg/kg) with fixing indicators (appearance, behavior, condition of the body hair coat, water and food consumption, excretion, body weight and its growth) during 14 days. After the animals were withdrawn from the experiment, autopsy, macroscopic evaluation and weighing of the internal organs were performed.
The results showed that with the introduction of the test substance into the animal organism, death during the observation period (14 days) did not occur. It was not possible to determine the semi-lethal dose for the test compound.
Conclusion. The conducted studies allow us to conclude that this substance is practically non-toxic and can be classified as hazard class V. Further research will be directed to the formation of hydrogel compositions with medicinal substances.

1. Wu DQ, Zhu J, Han H, Zhang JZ, Wu FF, Qin XH, et al. Synthesis and characterization of arginine-NIPAAm hybrid hydrogel as wound dressing: In vitro and in vivo study. Аcta biomaterialia. 2018; 65: 305-316. doi: 10.1016/j.actbio.2017.08.048

2. Viezzer C, Mazzuca R, Machado DC, Forte MMD, Ribelles JLG. A new waterborne chitosan-based polyurethane hydrogel as a vehicle to transplant bone marrow mesenchymal cells improved wound healing of ulcers in a diabetic rat model. Carbohydrate polymers. 2020; 231: 115734. doi: 10.1016/j.carbpol.2019.115734

3. Ochirov OS, Razuvaeva YG, Badmaev NS, Stelmakh SA, Mognonov DM. Wound-healing effect of polyguanidine-based hydrogel. Acta biomedica scientifica. 2016; 1(5): 117-120. doi: 10.12737/23405 (in Russ.)

4. Lebedeva SN, Ochirov OS, Stelmakh SA, Grigoryeva MN, Zhamsaranova SD, Mognonov DM. Wound healing effect of polyhexamethylene guanidine hydrochloride hydrogelat burns. Acta biomedica scientifica. 2017; 2(4): 93-96. doi: 10.12737/article_ 59fad51d481658.42549272 (in Russ.)

5. Oule MK, Azinwi R, Bernier AM, Kablan T, Maupertuis A-M, Mauler S, et al. Polyhexamethylene guanidine hydrochloride-based disinfectant: a novel tool to fight meticillin-resistant Staphylococcus aureus and nosocomial infections. Journal of Medical Microbiology 2008; 57(12): 1523-1528. doi: 10.1099/jmm.0.2008/003350-0

6. Rose K-N, Ama LM, Kablan T, Yao CYB, Oule MK, Koussemon M. Assessment of the antifungal activities of polyhexamethylene-guanidine hydrochloride (PHMGH)-based disinfectant against fungi isolated from papaya (Carica papaya L.) fruit. African Journal of Microbiology Research. 2011; 5(24): 4162-4169. doi: 10.5897/AJMR11.608

7. Kim BR, Anderson JE, Mueller SA, Gaines WA, Kendall AM. Literature review - efficacy of various disinfectants against Legionella in water systems. Water Research. 2002; 36(18): 4433-4444. doi: 10.1016/s0043-1354(02)00188-4

8. Munoz-Bonilla A, Fernandez-Garcia M. Polymeric materials with antimicrobial activity. Progress in Polymer Science. 2012; 37(2): 281-339. doi: 10.1016/j.progpolymsci.2011.08.005

9. Feng L, Wu F, Li J, Jiang Y, Duan X. Antifungal activities of polyhexamethylene biguanide and polyhexamethylene guanide against the citrus sour rot pathogen Geotrichum citri-aurantii in vitro and in vivo. Postharvest Biology and Technology. 2011; 61(2): 160-164. doi: 10.1016/j.postharvbio.2011.03.002

10. Ochirov OS, Stel’makh SA, Mognonov DM. Hydrogels based on polyalkiylguanidines and aldehydes. Polymer Science Series B. 2016; 58: 334-340. doi: 10.1134/S1560090416030106