Dual delivery of tuberculosis drugs via cyclodextrin conjugated curdlan nanoparticles to infected macrophages

In tuberculosis, macrophages serve as a host for Mycobacterium tuberculosis and hence targeting them with nanoparticles-based drug delivery could be the best strategy to achieve high therapeutic efficacy. Two tuberculosis drugs, namely rifampicin and levofloxacin, which have different mechanism of action on the bacteria, were complexed with cyclodextrin and conjugated to curdlan nanoparticles, to achieve simultaneous sustained release of both the drugs over a prolonged period of time. They are non-cytotoxic to both RAW 264.7 and L929 cells. They are taken up (similar to)1.8 times more by the macrophage cells through dectin-1 receptor than the fibroblast cells. They are also able to kill more than 95% of Mycobacterium smegmatis residing within the macrophages in 4 h. These results demonstrate that curdlan-CD nanoparticles can be a promising system for the loading and intracellular release of hydrophobic drugs into macrophages for various therapeutic applications.