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Journal of Antimicrobial Chemotherapy (1994) 33, 265-271
© 1994 The British Society for Antimicrobial Chemotherapy

research-article

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

P. R. J. Gangadharama, S. Kailasama, S. Srinivasana and D. L. Wiseb

University of Illinois College of Medicine at Chicago 835 S. Wolcott, Room E709, Chicago, Illinois 60612 bNortheastern University, Chemical Engineering Department Boston, MA 02115, USA

Received 28 January 1993; accepted 22 September 1993

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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