Membrana bioativa de colágeno contendo hesperidina em lipossomas promove cicatrização de feridas em modelo experimental de ferida cutânea aberta

Abstract

Flavonoids are a class of compounds with a wide variety of biological functions, being an important source of new products with pharmaceutical potential, including in the treatment of skin wounds. Thus, the work aimed to evaluate the healing potential of flavanoids and medicinal plants, especially flavonoids, on wound healing. In order to gather evidence in the literature regarding the healing properties of flavonoids in skin wounds using animal models, a systematic review was carried out through a specialized search in four databases: PubMed, Scopus, Web of Science and Embase, resulting in fifty and five (55) articles that met the established inclusion and exclusion criteria. In this review, flavonoids showed effects in relation to the inflammatory process, angiogenesis, re-epithelialization and oxidative stress. They have been shown to be capable of acting on macrophages, fibroblasts and endothelial cells by mediating the release and expression of TGF-β1, VEGF, Ang, Tie, Smad 2 and 3 and IL-10. Furthermore, they were able to reduce the release of inflammatory cytokines, NFκB, ROS and the M1 phenotype. Flavonoids acted to positively regulate MMPs 2, 8, 9 and 13, and the Ras/Raf/MEK/ERK, PI3K/Akt and NO pathways. Subsequently, a pre-clinical trial was carried out using 72 Rats (Wistar) that were subjected to skin excision using an 8 mm metal punch, and randomized into groups according to treatment: no intervention - (SI); control - collagen membrane containing liposomes (COL) and collagen membrane containing hesperidin in liposomes (COL/HESP) – product already deposited with INPI BR 10 2023 023131 4. The wound areas were measured using a digital caliper on the 3rd, 7th, 14th and 21st day post-injury and evaluated histologically (hematoxylin-eosin staining) for the response and type of inflammatory infiltrate, granulation tissue, fibroblast proliferation, deposition of collagen fibers and re-epithelialization in the healing area. Differences between groups were analyzed using the Analysis of Variance test, one way, followed by Tukey's post- test. The results were expressed as mean ± S.E.M. and considered significant when p<0.05. In the analysis of the wound reduction area, animals treated with COL/HESP significantly increased the percentage of wound reduction on the 3rd day when compared to the SI group (p<0.01) and on the 7th day when compared to the SI groups (p <0.001) and COL (p<0.001). When evaluating the intensity of the inflammatory reaction, COL/HESP reduced the inflammatory profile on the 3rd day when compared to the SI groups (p<0.01) and on the 7th day when compared to the SI (p<0.01) and COL (p <0.05), respectively. In the histomorphological analysis, COL/HESP significantly increased the epithelialization rates of residual wounds on the 3rd day when compared to the SI (p<0.01) and COL (p<0.05) groups and on the 7th day when compared to the SI groups ( p<0.001) and COL (p<0.01). It is concluded, therefore, that flavonoids, such as hesperidin, represent a promising, innovative biotechnological alternative with great potential for the treatment of wounds.0.01) and on the 7th day when compared to the SI (p<0.01) and COL (p<0.05), respectively. In the histomorphological analysis, COL/HESP significantly increased the epithelialization rates of residual wounds on the 3rd day when compared to the SI (p<0.01) and COL (p<0.05) groups and on the 7th day when compared to the SI groups (p<0.001) and COL (p<0.01). It is concluded, therefore, that flavonoids, such as hesperidin, represent a promising, innovative biotechnological alternative with great potential for the treatment of wounds.