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Toxicological evaluation of anisotropic cross-linked polyvinyl alcohol hydrogels intended for humic substances immobilization and topical skin disease treatmentстатья
- Авторы: Igumnova A., Artyukhov A., Tikhonova T., Kuskov A., Charvalos E., Docea A.O., Tsatsakis A.
- Журнал: Toxicology Letters
- Том: 399
- Год издания: 2024
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: S244
- DOI: 10.1016/j.toxlet.2024.07.593
- Аннотация: Most skin diseases and wounds progress through four main phases of healing: coagulation, inflammation, proliferation and remodeling. The prolonged inflammation stage leads to chronic skin diseases and wounds which are usually characterized by disorders of skin microbiome, high oxidative stress and are additionally infected with biofilm bacteria, creating additional barriers to wound healing [ 1 ]. The most prospective way to treat such chronic skin diseases is topical dressings with antioxidants and antimicrobial substances combinations and simultaneous photothermal therapy features [ 2 ]. In the current study, we propose biocompatible polyvinyl alcohol (PVA) cross-linked hydrogels as a base for new topical skin disease remedies, in combination with humic substance complexes as prospective candidates with antioxidant and anti-inflammatory activities, possibly combined with light-based photothermal therapy. Humic substances (HS) are natural organic high-molecular compounds with a wide range of biological effects [ 3 ]. To use HS as components for novel skin disease treatment hydrogels, the key task is to study their safety and biological effects. Several studies have shown that HS does not have a toxic effect on the organs and systems of experimental animals, which makes them promising targets for our further investigations [ 4 ]. By now, we have prepared hydrogels from PVA acylated derivative with a content of unsaturated groups of 4.5%. The concentration of the polymer solution was 10%. The “hydrogen peroxide – Mohr's salt” system was used as the initiator of radical polymerization during cross-linking. To assess the toxicity of the hydrogel samples obtained as a result of cross-linking, a set of methods was used, such as: studying hemolytic activity (hemolytic test), and cytotoxic action while determining the toxicity index when exposed to a biological cellular test object. The hemolytic effect of aqueous extracts was assessed in in vitro experiments with isolated rabbit erythrocytes. The percentage of hemolysis of extracts of all samples did not exceed values from 0 to 0.15%, with an acceptable value of 2%. Cytotoxicity was assessed on a short-term suspension culture of motile germ cells prepared from frozen cattle semen and no negative impact on the viability of the cell test was observed (toxicity index was 75.0–88.0%). The acute toxicity, irritant and sensitizing activity of the polymer hydrogel samples were evaluated in vivo on mice. The animal experiment was carried out according to all needed ethical rules and sanitary standards. No death or external manifestations of intoxication were registered. There was no skin reaction at the application sites and at the site of preliminary sensitization and provocative intradermal test. The prospective investigations will be directed to the preparation of HS-loaded PVA cross-linked hydrogels and highlighting their therapeutic potential as a topical remedy for skin disease treatment
- Добавил в систему: Артюхов Александр Анатольевич