Current treatment of tuberculosis is inadequate due to lengthy treatment course and drug-related toxicity. To address these setbacks, we developed a nanotechnology drug delivery system that can be administered in a single dose that maintains an active level of drug for at least a week. Polymeric poly(lactic-co-glycolic acid) nanoparticles of 200-300 nm were synthesized, with a drug encapsulation efficiency of 50-65% for isoniazid and rifampicin. The particles were taken up in vitro and in vivo and a slow release profile was observed in mice over 5 days. This study illustrates the feasibility of a sustained release system for tuberculosis treatment.