Paper Title
Nanoparticle Formulation of Two Anti-TB Drugs for The Treatment of Multidrug Resistant Tuberculosis

Abstract
Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles are readily internalised into macrophages and leads to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into alginate entrapped PLGA nanoparticles. The alginate entrapped PLGA nanoparticles were within the desirable particle size range of 312-365 nm and the PDI was 0.14-0.31, and therefore were chosen for subsequent studies. Alginate entrapped nanoparticles exhibited an entrapment of moxifloxacin range of10.1-18.7 μg/mg and an entrapment of amikacin range of15-17.4μg/mg. To study the macrophage uptake efficiency, both formulations of the alginate entrapped nanoparticle; non-calcium formulation and calcium wereloaded with coumarin-6 as a marker, seeded toH37RA infected THP-1 derived macrophages and examined by confocal microscopy. The alginate entrapped particles were readily internalised into the macrophages and highly concentrated in the perinuclear region, and the non-calcium alginate entrapped formulation showing the maximum internalisation. Furthermore, the anti-mycobacterial activity of the dually entrapped drug-loaded particles (moxifloxacin and amikacin) was evaluated using M. tuberculosis-infected macrophages, which revealed anenhanced inhibition of viable bacterial count compared to single drug loaded nanoparticle formulations, and tothe untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.