Chemotherapy of Mycobacterium tuberculosis infections in mice with a combination of isoniazid and rifampicin entrapped in Poly (DL-lactide-co-glycolide) microparticles.

Strategies to improve patient compliance in tuberculosis chemotherapy include the use of sustained release drug delivery systems. In this study, Poly (DL-lactide-co-glycolide) (PLG) microparticles containing a combination of isoniazid and rifampicin were developed as sustained release carrier systems. A single dose of PLG microparticles exhibited a sustained release of isoniazid and rifampicin in vivo up to 7 and 6 weeks, respectively. Free drugs (in combination) injected in the same doses were detectable in vivo up to 24 h only. One dose of PLG microparticles cleared bacteria more effectively from lungs and liver in an experimental murine model of tuberculosis after low-dose PLG combination drug therapy and in liver after high-dose PLG combination drug therapy as compared with a daily administration of the free drugs. These results suggest that PLG microparticles offer an improvement for tuberculosis chemotherapy over the conventional treatment.