Inhalable microparticles containing isoniazid and rifabutin target macrophages and 'stimulate the phagocyte' to achieve high efficacy.
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.
Yadav
Awadh Bihari
AB
Pharmaceutics Division, Central Drug Research Institute, Lucknow 226 001, India.
Sharma
Rolee
R
Muttil
Pavan
P
Singh
Amit Kumar
AK
Verma
Rahul Kumar
RK
Mohan
Mradul
M
Patel
Sanjay Kumar
SK
Misra
Amit
A
D000280:Administration, Inhalation; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology; D053938:DNA Fragmentation; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010316:Particle Size; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D017828:Rifabutin / Q000008:administration & dosage / Q000494:pharmacology; D014376:Tuberculosis / Q000276:immunology
D000995:Antitubercular Agents; D017828:Rifabutin; D007538:Isoniazid