Tuberculosis (TB) is a chronic infectious disease that represents one of the greatest global public health challenges, especially in light of the increasing prevalence of resistant strains. Triazole-class molecules have been widely studied as promising candidates for new therapeutic agents. However, many of these structures’ present physicochemical limitations, such as low solubility and high cellular toxicity. Nanoencapsulation emerges as a strategy capable of enhancing efficacy and reducing compound toxicity. Therefore, this study aimed to develop and characterize PLGA nanoparticles containing a triazole molecule and to compare antimycobacterial activity and cytotoxic profile of the nanoparticle and free compound against Mycobacterium tuberculosis (Mtb). Polymeric PLGA nanoparticles containing compound 173 were obtained by double emulsification and characterized by average diameter (Z-Ave), polydispersity index (PdI), zeta potential (ZP), and encapsulation efficiency (EE%) using DLS and UV-VIS, respectively. Antimycobacterial activity was evaluated by 96-well plate microdilution assay against strain H37Rv and a pre-XDR clinical isolate of Mtb. Cytotoxicity was determined in murine macrophages J774A.1 using the MTT assay. Nanoparticles presented Z-Ave of 182.4±0.86 nm, PdI of 0.011±0.07, ZP of -4.6±0.65 mV, and EE% of 33%. Free compound 173 showed minimum inhibitory concentration (MIC) of 4 µg/mL for strain H37Rv and 8 µg/mL for the pre-XDR isolate. In contrast, the nanoformulation showed no significant activity (MIC >128 µg/mL), indicating possible drug release limitation. Regarding cytotoxicity, the nanoformulation was less cytotoxic, with cell viability ranging from 45% to 99.99%, depending on concentration, compared to the free compound (11% to 95%). Nanoencapsulation of triazole derivative 173 significantly reduced cytotoxicity, demonstrating potential as a safer therapeutic alternative. However, further adjustments are needed to ensure effective drug release and preservation of antimycobacterial activity observed in the free molecule.
Laet et al. (Sun,) studied this question.