The effect of formulation variables on drug loading of antitubercular drugs in nanoparticle formulations

The current treatment regimen for pulmonary tuberculosis often results in toxicity and poor patient compliance leading to treatment failure and the development of drug resistance. Virulent Mycobacterium tuberculosis primarily targets and accumulates in macrophages where it has evolved several survival strategies leading to the persistence of the infection in the body. Thus, macrophages represent a niche for M. tuberculosis. Here, we report the development of a nanoparticle platform with potential for targeting the niche of Mycobacteria tuberculosis and achieve high drug concentrations at the biophase. PEGylated poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles encapsulating rifampicin, moxifloxacin and pyrazinamide have been developed. Nanoparticles were prepared using the water-in-oil-in-water double emulsification method. Poly(vinyl alcohol) was used as a stabilizer. The nanoparticles were characterized. Results show that formulation variables such as the concentration of stabilizer, feed amount of drug and the ratio of the aqueous to organic phase affect nanoparticle drug loading. The data suggest that these nanoparticles may provide a mechanism for targeting the niche of Mycobacteria tuberculosis and allow reduction in dosing frequency or increase in the dosing interval required to improve treatment adherence and therapeutic outcomes.