Potencial atividade antibacteriana de complexos de inclusão entre ciclodextrinas e farnesol: uma investigação tecnológica, científica e experimental

Abstract

Bacterial resistance is a significant threat to public health and the global economy. Therefore, the search for natural and safe alternatives has led to interest in compounds, such as farnesol, due to its antibacterial activity. However, the hydrophobicity and low retention present in these compounds restrict their medical application. Therefore, the encapsulation of farnesol in CDs emerges as a promising strategy to improve its physicochemical properties, therapeutic applicability and safety. Thus, the objective of this study was to conduct a patent search and a systematic review on the complexation of CDs with antibacterial agents, in addition to developing inclusion complexes between β-CD, HP-β-CD and farnesol. From this perspective, the reviews were carried out without publication date restrictions, which resulted in a final selection of 37 patents and 27 scientific articles. Both proposed the complexation of antibiotics that are already used on the market, natural products and synthetic substances. Furthermore, the studies mapped aspects and characteristics in relation to the type of CDs used, complexation techniques, characterization methods and main species of microorganisms used in experimental studies. According to the scenario obtained in technological and scientific investigations, the experimental study was based on the preparation of inclusion complexes by the freeze-drying method and their physicochemical characterization, through calorimetric techniques, FTIR, XRD, SEM, TT% and EC % and Determination of pHpzc. In vivo toxicity was determined by the alternative model of Tenebrio molitor larvae, obtaining the median lethal dose and the toxic dose of the samples. Furthermore, the potential interaction of the complex with serum albumin was evaluated through fluorescence suppression tests and antibacterial activity. The complexation of farnesol was evidenced with β-CD and HP-β-CD by the characterization techniques, EC% (73.53% and 74.12%, respectively) and pHpz (7.4 and 7.7, respectively). Inclusion complexes demonstrated higher LD50 (125 and 300mg/kg, respectively) and toxic dose (850 and 1000mg/kg, respectively) compared to free farnesol (LD50 of 25mg/kg and toxic dose of 200mg/kg), in addition to induce conformational changes in albumin. In terms of antibacterial activity, the farnesol/HP-β-CD complex (8μg/mL) against the Staphylococcus aureus ATCC 25923 strain showed a decrease in the minimum inhibitory concentration compared to free farnesol and the farnesol/β-CD complex. (16μg/mL). In this way, the complexation of farnesol in CDs was proven during the characterization tests, demonstrating the compatibility of these substances and the potential use of inclusion complexes in the production of new therapeutic alternatives in the pharmaceutical industry. Therefore, faced with the global challenge posed by resistant pathogens, there is an urgent need to develop new antibacterial agents or modify existing ones, as these efforts are essential to effectively combat the growing threat of antimicrobial resistance.