Delivery of rifampicin–PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis

Inhalation delivery of poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP–PLGA MS) to alveolar macrophage (Mϕ) cells could be an effective drug delivery system for the treatment of tuberculosis. To examine this possibility, we studied (1) the bactericidal effect of RFP–PLGA MS on Mycobacterium bovis Bacillus Calmette–Guérin (BCG)-infected rat alveolar Mϕ NR8383 cells, and (2) changes in the biochemical events induced in these cells by the uptake of RFP–PLGA MS. The amount of intracellular RFP imported into the Mϕs by RFP–PLGA MS containing 0.25 and 2.50 μg RFP/mL was more than twice and ten times, respectively, than that attained with 5.00 μg/mL of RFP solution; and the MS exerted more potent bactericidal effect on BCG inside Mϕ cells than 5.00 μg RFP/mL solution after incubation for 7 days. RFP–PLGA MS little affected the viability of Mϕ cells, whereas the polystyrene latex (PSL) MS used as a reference decreased it significantly. RFP–PLGA MS did not stimulate the production of tumor necrosis factor-α (TNF-α), nitric oxide, interleukin-10 (IL-10), and transforming growth factor-β1 (TGF-β1) by the Mϕ cells, whereas PSL MS stimulated all of these mediators except IL-10. We conclude that RFP–PLGA MS are bio-safe microspheres due to their “silent” nature when taken into Mϕ cells and that they are promising for the treatment of tuberculosis by pulmonary inhalation. Rifampicin (RFP) incorporated in poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) was efficiently imported into Mϕ cells, and the MS exerted potent bactericidal effect on BCG inside Mϕ cells. [Display omitted]