Chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub-therapeutic dose against experimental tuberculosis.

The present study was designed to evaluate the chemotherapeutic efficacy of poly (DL-lactide-co-glycolide) (PLG) nanoparticles (NP) encapsulating three front-line antitubercular drugs (ATDs: rifampicin, RIF; isoniazid, INH and pyrazinamide, PZA) at 2/3rd therapeutic dose. PLG nanoparticles prepared by the double emulsion and solvent evaporation technique were administered orally at 2/3rd therapeutic dose to guinea pigs. A single oral administration of the formulation resulted in sustained drug levels in the plasma for 7-12 days and in the organs for 11-14 days with a significant improvement in mean residence time as well as drug bioavailability. The administration of PLG nanoparticles every 10 days (five doses) to Mycobacterium tuberculosis H(37)Rv infected guinea pigs led to undetectable bacilli in the organs, as did 46 conventional doses. Therefore, nanoparticle based antitubercular chemotherapy forms a sound basis for a reduction in dosing frequency and also offers the possibility of reducing the drug dosage.