Obtenção de nanohíbridos a partir da montmorilonita para aplicação na liberação modificada de fármacos tuberculostáticos

Abstract

Tuberculosis (TB) is a severe infectious disease and one of the leading causes of preventable deaths worldwide. TB treatment is complex, involving multiple drugs, such as isoniazid (INH) and rifampicin (RIF), which present severe side effects due to the high dosages required. These adverse effects are among the factors that compromise treatment adherence, potentially leading to the emergence of multidrug-resistant bacterial strains. In this context, the search for new drug delivery strategies is crucial to improve treatment efficacy and reduce side effects. Clay-drug nanohybrid systems have gained prominence in the literature due to their potential to enhance the bioavailability of biomolecules, including drug protection against degradation and promoting controlled and pH-responsive release. This study aimed to develop montmorillonite nanohybrids, as well as bionanocomposites incorporating polysaccharides, for the modified release of tuberculostatic drugs, aiming to mitigate the severe side effects associated with these medications. Montmorillonite was used in its natural form and associated with the polysaccharides carboxymethyl cellulose (CMC) and the polysaccharide extracted from chia seeds (Salvia hispanica L.). In the first stage, the montmorillonite-rifampicin nanohybrid was obtained and tested for pHresponsive release of the drug. A 24 factorial design was applied to optimize the rifampicin incorporation process, identifying pH as the most influential variable. The optimized drug incorporation dose was 9860 ± 1,21 mg/g, and in vitro release studies demonstrated controlled release of 70% of the drug after 16 hours in simulated intestinal fluid. Kinetic analysis indicated prolonged release, fitting the Higuchi model. In the second stage, isoniazid was incorporated into montmorillonite, followed by the preparation of bionanocomposites coated with CMC and chia polysaccharide. The isoniazid incorporation efficiency was optimized through experimental design, and the materials obtained were characterized using techniques such as XRD, FTIR, TGA, and SEM. In vitro release studies confirmed the potential of the bionanocomposites for prolonged and controlled drug release at different pH levels, simulating the gastrointestinal environment. The results indicate that the developed nanohybrids and bionanocomposites are promising for the modified release of tuberculostatic drugs, presenting robust physical and chemical stability, as well as controlled release, which can reduce toxicity and side effects associated with conventional treatment.