Treatment of Tuberculosis Using a Combination of Sustained-Release Rifampin-Loaded Microspheres and Oral Dosing with Isoniazid

摘要: Previously, we reported on the use of rifampin-loaded microspheres to effectively treat Mycobacterium tuberculosis-infected macrophages and mice. Using similar biocompatible polymeric excipients lactide glycolide copolymers, have increased rifampin loading small microsphere formulations (1 10 μm) by fourfold. Improved were evaluated individually in combination with oral regimens isoniazid for treatment tuberculosis H37Rv-infected Groups (10 mice per group) consisted that received (i) dosages (25 0.19 mg/kg body weight/day), (ii) two intraperitoneal injections days 0 7, (iii) a 7 orally 25 (12.5 0.39 mg/kg/day), (iv) placebo injections, (v) no treatment. Treatment alone resulted significant reductions numbers CFU lungs spleens day 26. A bioassay revealed plasma levels from exceeded MICs more than twofold throughout 26-day experimental period. Susceptibility testing demonstrated continued sensitivity during Whereas significantly reduced ranging 12.5 1.56 mg/kg, therapy effective range mg/kg. In many cases, complete elimination was obtained therapy, something not achieved most single therapies. These results demonstrate ability achieve murine model also them safely another antimycobacterial agent.