Weekly pulmonary delivery of β-glucan-chitosan-poly(lactic co-glycolic) acid (β-C-P) nanoparticles with daily standard oral therapy achieves control of <i>Mycobacterium tuberculosis</i> in BALB/c mice

ABSTRACT Prolonged daily tuberculosis therapy contributes to toxicity, poor adherence, and drug resistance. We developed rifampin (RIF)-loaded β-glucan-chitosan-poly (lactic co-glycolic) acid nanoparticles (β-C-P nanoparticles) for weekly pulmonary delivery and evaluated a hybrid dosing regimen in a BALB/c Mycobacterium tuberculosis model. Weekly instilled RIF loaded 20% β-C-P nanoparticles combined with daily oral isoniazid (INH) and pyrazinamide (PZA) reduced lung and spleen bacterial burdens comparable to oral daily standard of care (RIF, INH, PZA) and were well tolerated, demonstrating preserved efficacy with reduced RIF dosing frequency.