Estudo da liberação da vancomicina em hidrogel quitosana/genipina para uso na prevenção de bactéria em implantes biomédicos.

Abstract

The proposal to use a controlled release system as an alternative to conventional treatments aimed at administering antibiotics has gained strength in recent decades. The chitosan-based hydrogel, an antimicrobial biopolymer, offers the possibility of controlling the release of the drug when it is cross-linked by agents such as genipin. However, knowledge about the characteristics involved, such as the rate and mass transport mechanisms, involved in the controlled release of vancomycin in chitosan hydrogel is still limited. Given the above, the objective of this work is to synthesize a polymeric chitosan / genipin matrix to evaluate the characteristics regarding the rate and the mechanisms of mass transport involved in the control of vancomycin release over time. For this purpose, an aqueous solution of chitosan 1.5% (w/v) in lactic acid was prepared, keeping under stirring on a magnetic stirrer and for comparison purposes the addition of the crosslinking agent genipin and the drug vancomycin was performed by three procedures: the first was adding vancomycin together with genipin (H1), and the second and third method was adding vancomycin before crosslinking (H2), and after crosslinking the base solution (H3). The samples were characterized by Fourier transform infrared spectroscopy (FTIR); X-ray diffraction (XRD), and thermogravimetric analysis (TG) and finally, the vancomycin release test in the hydrogel, analysis of variance (ANOVA) and the Tukey test or t test with a 5% probability significance were performed with the help of the statistical software PAST version 3.23 (Hammer et al., 2001) and mathematical models. Based on the results it was possible to observe that the FTIR spectra showed the characteristic bands of the

studied materials. The XRD diffractograms confirmed the formation of the semi- crystalline phases of chitosan and crystalline of the genipin. Vancomycin proved to

be amorphous. Through the results obtained in the thermogravimetric analyzes, it was possible to observe thermal behaviors characteristic of the studied materials. Confirmed by the appearance of events that are characteristic of mass changes in the material upon exposure to temperature. Through the kinetic profile of the vancomycin drug release, it can be observed that the release occurs more quickly at the beginning, up to 150 minutes, and that then this release becomes slower until the end of the observed time of 300 minutes. From the analysis of variance (ANOVA) and the Tukey test, it was possible to observe that the order in which vancomycin is added to the hydrogel carrier system is not a major factor in altering or modifying the final quantity released, as well as the storage period. Regarding the study of drug release kinetics, it predicted a Fickian mechanism based on diffusion. We can conclude that from the tests carried out, that the use of a carrier system based on chitosan and genipin for controlled release of vancomycin occurs promisingly, since it will possibly prevent adhesion, colonization and subsequent bacterial proliferation.