Clofazimine nanoclusters show high efficacy in experimental TB with amelioration in paradoxical lung inflammation

Breaking barriers: The potential of nanosystems in antituberculosis therapy

“…Changes in autophagy and ferroptosis markers in BCG-infected macrophages Female C57BL/6J mice, 500 mg/(kg⋅day) Worsening of lung lesions and increased inflammatory cytokines. Ferroptosis blocker reduced inflammation [ 244 ] Clofazimine Nanocrystals (CLF-NCRs) ∼600 MIC of ∼0.62 μg/mL BALB/c mice, oral administration 25 mg/kg Significant reduction in CFU and improvement in lung histology after 30 days with CLF-NCRs [ 245 ] Amorphous Nanoparticles (BDQ/BTZ) 60 ± 13 (BDQ), 62 ± 44 (BTZ) Ability to penetrate biological barriers and reach intracellular locations of mycobacteria C3HeB/FeJ mice, Intranasal administration 6.56/6.72 mg/kg High concentrations of BDQ/BTZ in lung granulomas with minimal presence in spleen or liver [ 246 ] CS-PLGA -β-glucan Nanoparticles (CS-PLGA@GL) ∼217 Increased gene expression for specific cytokines at certain β-glucan concentrations. ROS production and specific protein secretion also increased.…”

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression

“…The administration of inhaled treatment resulted in the attenuation of pro-inflammatory mediators, such as cytokines (TNF-α and IL-6) and MMP-2,9, in BALF and lung tissue homogenates. 178 Conclusively, studies on drug delivery methods and the therapeutic release of MMP inhibitors in TB pathogenesis are scarce. Therefore, it is crucial to synthesize different drug delivery mechanisms and develop various formulations involving MMP inhibitor molecules, alone or combined with TB antibiotics.…”

“…Furthermore, our research group synthesized nanoclusters of clofazimine, exhibiting notable efficacy in experimental TB and a concurrent improvement in paradoxical lung inflammation. The administration of inhaled treatment resulted in the attenuation of pro-inflammatory mediators, such as cytokines (TNF-α and IL-6) and MMP-2,9, in BALF and lung tissue homogenates . Conclusively, studies on drug delivery methods and the therapeutic release of MMP inhibitors in TB pathogenesis are scarce.…”