Efeitos farmacológicos da triancinolona associada à cola cirúrgica na cicatrização de feridas cutâneas em ratos Wistar

Abstract

Introduction: The surgical glue of 2-octyl-cyanoacrylate is widely used in the closure of cutaneous surgical wounds. However, side effects such as contact dermatitis, dehiscence, and scar alterations are common and caused by the polymer itself. Exogenous corticosteroids are widely employed for their anti-inflammatory and immunomodulatory properties. Objectives: To evaluate macroscopically and microscopically the pharmacological effects of the corticosteroid triamcinolone acetonide (TA) incorporated into 2-octyl-cyanoacrylate surgical glue (C+TA) in the initial phase of the surgical wound healing process in Wistar rats. Material and Methods: TA corticosteroid was added to the surgical glue (C) and characterized physicochemically by different methods such as Release Assay (RA), Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Through in vivo studies, the effects of the healing process, glue, or C+TA on the same rat were evaluated by macroscopic and microscopic analyses (histology and immunohistochemistry) on postoperative days 7 and 14. Results: RA showed release of TA added to the glue at concentrations of 5mg/mL, 10mg/mL, and 20mg/mL up to 120h. In FTIR, it was observed that there was no interaction between TA molecules and the glue, however, the presence of the drug was identified at a concentration of 20mg/mL, chosen for the in vivo phase. TGA analysis showed that the addition of TA corticosteroid to the glue did not alter the thermal resistance of this polymer, as well as the DSC assay did not alter the thermal events of the glue to cause instability, being able to coexist safely. However, in SEM there was a loss of glue homogeneity. In the in vivo studies, macroscopically, there was no alteration in the coaptation of the edges, secretion, dehiscence, infection, or difference in the healing of all rats that maintained the dressing. In histology, with Hematoxylin-eosin staining, the following parameters were significantly different (p <0.05): less fibrosis in the C+TA treatment (14 days); less neovascularization in C+TA (7 days); a higher presence of macrophages in the C+TA treatment (14 days) and higher presence of neutrophils in the C+TA treatment (7 days). With Masson's Trichrome staining, collagen fibers were more expressive in the C+TA treatment (7 and 14 days, p> 0.05). Immunohistochemical analysis did not yield statistically different results, however, with the CD68 marker, discrete increase in macrophages was observed in the C+TA treatment (7 and 14 days); with the α-SMA marker, more myofibroblasts were observed in the C+TA treatment (7 days) and less in the C+TA (14 days) and a discrete increase in the presence of fibronectin in the C+TA treatment (7 and 14 days). Conclusion: The combination of 2-octyl-cyanoacrylate with triamcinolone has promising potential in translational medicine and may be a new biomaterial to be considered for new preclinical and clinical tests, since there were no alterations in the physicochemical characteristics in the tests performed. In addition to confirming the anti inflammatory and immunomodulatory effects of the corticosteroid, attenuating the inflammatory phase of healing, and providing adequate remodeling of the extracellular matrix and recomposition of tissue functional activity