Complexo de ródio (III) com policiclodextrina: síntese, caracterização e avaliação da sua atividade em sistemas biológicos

Abstract

The treatment of inflammatory diseases faces major challenges related to the unwanted effects of currently available anti-inflammatory drugs, in addition to the lack of drugs to treat chronic inflammatory and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, among others. Therefore, the development of new pharmacological agents becomes necessary. In this context is important to highlight that nanomedicine has tools that allow the development of controlled drug release systems using nanostructures like cyclodextrins. Cyclodextrins stand out in this context for their excellent biocompatibility and ability to form coordination complexes, however, in complex formulations, there may be dissociation of the compounds due to competition with other chemical species present in the medium. The polymerization of cyclodextrins represents a strategy to increase their complexation capacity. Rhodium is one of the metals that make up the platinum group and knowledge about its antitumor effect has existed for several decades due to the cytotoxic activity of transition metals, however, in recent years the possible antiinflammatory activity of this class of metals has been investigated. Thus, the present study aimed to synthesize, characterize and evaluate the biological activities of the rhodium(III) coordination complex with polycyclodextrin. The structural characterization was performed by infrared spectroscopy, by which it was possible to observe changes in various vibrational modes of pCD after the formation of the complex; 1H nuclear magnetic resonance, which confirmed the intermolecular interactions that occurred during the formation of the complex by variations in the chemical shift of the hydrogen signals. Isothermal calorimetric titration showed that the complexation is driven by enthalpy and entropy, with 1:3 stoichiometry. The evaluation of in vitro biological activities was carried out through cytotoxicity and genotoxicity assays, determination of nitric oxide production and evaluation of the expression of the transcription factor NF-ĸB and showed that the synthesized complex promoted a decrease in nitric oxide production and NF-ĸB expression in macrophage strains RAW 264.7 and J774A.1 maintaining cell viability and without promoting damage to its genetic material. For in vivo evaluation, models of induction of paw edema in mice by inoculation of carrageenan (acute inflammation) and by inoculation of ovalbumin (delayed hypersensitivity) were used. The results showed that rhodium promoted the reduction of paw edema in a similar way to dexamethasone. It was also shown that the complex promoted the reduction of paw edema, and that this fact is related to the potential of polycyclodextrin to optimize rhodium activity. Further studies should be carried out to evaluate the pathways that are involved in the anti-inflammatory activity of rhodium-based coordination complexes to enable the exploration of their potential.