The development of new bioactive compounds is a promising strategy against tuberculosis (TB), a disease caused mainly by Mycobacterium tuberculosis (Mtb). This approach becomes even more relevant given the increase in resistance to traditional drugs. Triazole derivatives emerge as relevant candidates due to their antimycobacterial potential. However, they face issues related to stability, bioavailability, and toxicity. Therefore, nanotechnology has been used to overcome these limitations, enabling not only drug targeting to the site of infection but also reduced cytotoxicity. This study compared the antimycobacterial efficacy and cytotoxic profile of triazole derivative 177 in free and nanoencapsulated forms in PLGA nanoparticles against Mtb strains. The nanostructured formulation containing compound 177 was obtained by double emulsification and characterized for mean diameter (Z-Ave), polydispersity index (PdI), zeta potential (ZP), and encapsulation efficiency (EE%) by DLS and UV-VIS spectrophotometry. Antimycobacterial activity was determined by a microdilution assay in 96-well plates against the H37Rv strain and a pre-XDR clinical isolate. The cytotoxicity profile was assessed in murine J774A.1 macrophages by the MTT assay. The nanoparticles showed Z-Ave of 183.9±1.06 nm, PdI of 0.019±0.01, ZP of -4.39±0.94 mV, and EE% of 57%. Free compound 177 showed MIC of 8 µg/mL against H37Rv and 16 µg/mL against the pre-XDR isolate, whereas the nanoformulation showed no detectable antimycobacterial activity at the tested concentrations (MIC >128 µg/mL) in either strain, indicating impaired drug release. On the other hand, there was a marked improvement in the cytotoxicity profile of the nanoformulation, with a significant increase in cell viability (55% to 99.99%), concentration-dependent, compared with the free form (11% to 95%). Although free compound 177 exhibited antimycobacterial activity against both drug-susceptible and drug-resistant Mtb strains, the nanoencapsulated form proved safer in terms of cellular toxicity. These data reinforce the potential of nanoencapsulation as a strategy to reduce adverse effects, highlighting the need for formulation adjustments to ensure efficient release and maintenance of antimicrobial activity.
Formiga et al. (Sun,) studied this question.