Desenvolvimento e caracterização de filmes de quitosana/álcool polivinílico contendo sulfadiazina de prata e um derivado n-acilidrazônico

Abstract

Skin comorbidities affect more than 600 million people each year and generate more than $ 1 billion in costs for healthcare systems worldwide. In Brazil, they were responsible for more than 700 thousand hospitalizations and 550 million reais in costs in 2020. These data reflect the absence of treatments with adequate characteristics such as oxygenation and temperature control, in addition to preventing infections, for example. In order to guarantee these requirements, biopolymers are widely used in curative formulations. Among these, chitosan (CHI) stands out, which despite the proven antimicrobial activity, in these clinical conditions, are not adequate. Therefore, the combination of an antimicrobial drug such as silver sulfadiazine (AgSD) and an N-acylhydrazonic anti-inflammatory (JR19) in CHI films can result in an extremely versatile dressing, given the flexibility of the films, by adding the polyvinyl alcohol (PVA), the antimicrobial activity of AgSD and anti-inflammatory of JR19. Thus, the work aimed to develop CHI+PVA films containing AgSD and the N-acylhydrazonic derivative JR19 as a new proposal for the treatment of skin wounds. Films without (F1), with AgSD 1 mg/JR19 8.6 mg (F2) and AgSD/JR19 1 mg (F3) were developed by the solvent evaporation technique and were characterized by the hemolytic potential, optical microscopy (OM), analysis microstructural, water vapor transmission rate (WVTR), photostability assay, foldable resistance, infrared spectroscopy (FTIR), in addition to the analytical validation of a spectrophotometric method for quantifying JR19 in films and preliminary studies to determine the antifungal activity against Candida albicans. The macroscopic characteristics revealed films with dispersion characteristics in the presence of drugs. The hemocompatibility results showed that all samples are classified as non-hemolytic (mean values equal to or less than 4.78%). The OM indicated that the drugs are homogeneously dispersed in the polymeric matrix with crystal sizes of 4.265 ± 3.402 and 6.385 ± 3.299 µm for F2 and F3, respectively. The mean surface roughness parameter did not change significantly in the presence of drugs. TTVA showed values of 1411.07 ± 61.69, 1349.51 ± 71.04 and 1352.78 ± 123.67 g m-2 day-1 for the F1, F2 and F3 films, respectively, which can prevent the maceration process, which represents an important parameter in the treatment of injuries associated with infections. The photostability test confirmed the photosensitive characteristic of AgSD and the need to use primary packaging with barrier properties against sunlight in the films. The presence of a greater amount of JR19 in film F2 reduced its foldable resistance in relation to F1 and F3. The absence of chemical incompatibility between the components was revealed by the FTIR. The spectrophotometric method for quantifying JR19 proved to be selective, linear, precise, accurate and robust. The F2 film showed good antifungal activity with inhibition of the growth of C. albicans by potentiating the activity of AgSD and CHI by a greater amount of JR19 compared to the F3 film. The preliminary results demonstrated that it was possible to develop and characterize films containing two drugs with antimicrobial and anti-inflammatory activities, however, future tests of the release profile and preclinical in vitro and in vivo tests of biological activity are necessary to prove the pharmacological efficacy.