alexa Delivery of rifampicin-PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis.
Infectious Diseases

Infectious Diseases

Journal of Infectious Diseases and Diagnosis

Author(s): Hirota K, Hasegawa T, Nakajima T, Inagawa H, Kohchi C, , Hirota K, Hasegawa T, Nakajima T, Inagawa H, Kohchi C,

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Abstract Inhalation delivery of poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP-PLGA MS) to alveolar macrophage (M phi) 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 M phi 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 M phi s by RFP-PLGA MS containing 0.25 and 2.50 microg RFP/mL was more than twice and ten times, respectively, than that attained with 5.00 microg/mL of RFP solution; and the MS exerted more potent bactericidal effect on BCG inside M phi cells than 5.00 microg RFP/mL solution after incubation for 7 days. RFP-PLGA MS little affected the viability of M phi 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-alpha (TNF-alpha), nitric oxide, interleukin-10 (IL-10), and transforming growth factor-beta1 (TGF-beta1) by the M phi 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 M phi cells and that they are promising for the treatment of tuberculosis by pulmonary inhalation. (c) 2009 Elsevier B.V. All rights reserved. This article was published in J Control Release and referenced in Journal of Infectious Diseases and Diagnosis

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