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Title: Inhalable microparticles containing isoniazid and rifabutin target macrophages and ‘stimulate the phagocyte’ to achieve high efficacy
Authors: Yadav, Awadh Bihari
Sharma, Rolee
Muttil, Pavan
Singh, Amit Kumar
Verma, Rahul Kumar
Mohan, Mradul
Patel, Sanjay Kumar
Misra, Amit
Keywords: Inhalable microparticles
Mycobacterium tuberculosis
Issue Date: Jun-2009
Publisher: CSIR
Abstract: Macrophage responses to infection with Mycobacterium tuberculosis (MTB) and treatment with soluble isoniazid (INH) plus rifabutin (RFB) versus microparticles containing equivalent amounts of drugs were compared. It was investigated whether macrophages driven to alternative activation upon infection with MTB could be rescued to display the classical activation phenotype. It was established that microparticles sustain high levels of drugs in cytosol of macrophages for longer period as compared to soluble drugs. Microparticles co-localized with intracellular bacteria, and induced a variety of innate bactericidal responses, including induction of free radicals, alteration of mitochondrial membrane potential and apoptosis. The data strongly suggest that additional benefit may be derived from the nature of the drug delivery system, which fulfils Koch’s dictum ‘stimulate the phagocyte’ for curing tuberculosis.
Description: 469-474
ISSN: 0019-5189
Appears in Collections:IJEB Vol.47(06) [June 2009]

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