Tuberculosis
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Nitric oxide (NO) kills Mycobacterium tuberculosis (Mtb) in vitro, but gaseous NO is difficult to administer to patients. We evaluated the consequences of intracellular delivery of NO using inhalable microparticles (MP) containing NO donors. MP containing 10% w/w of NO donors alone, or in addition to 25% each of isoniazid (INH) and rifabutin (RFB) in a polylactide-co-glycolide (PLGA) matrix were prepared by spray drying. ⋯ Inhalations of MP containing DETA/NO in combination with INH and RFB significantly (P < 10(-5), ANOVA) reduced cfu in lungs and spleens by 4 log. Gross morphology and histology of the lungs and spleen indicated that inhaled particles were well-tolerated. Inhalable MP containing NO donors need further investigation as an adjunct to standard anti-tuberculosis chemotherapy.