Experimental chemotherapy of tuberculosis using single dose treatment with isoniazid in biodegradable polymers

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Abstract
In previous studies we showed that a single implant of polylactic-co-glycolic acid (PLGA) polymer as a film containing isoniazid ensured sustained release of the drug for up to 4 weeks. These studies have been extended to PLGA polymer as a rod which is retrievable. Both types of implant gave therapeutically active levels of free isoniazid in liver and urine for prolonged periods. We assessed the in vivo chemo-therapeutic efficacy of the rod implant against heavy infections of virulent Mycobacterium tuberculosis in C57B1/6 mice. The chemotherapeutic data essentially confirmed the bioavailability data. In one chemotherapeutic study, one (7%) out of 15 mice which received the isoniazid polymer implant died within 30 days of bacterial challenge, while none of those receiving daily oral treatment died. In contrast, 14 (93%) of the 15 control mice died during the same period. In a second study similar results were obtained.

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