Improved rifampicin delivery to macrophages infected with Mycobacterium tuberculosis using folate targeted liposomes

Tuberculosis (TB) causes more deaths worldwide than any other infectious disease. The failure of TB control measures is exacerbated by drug resistance that continues to increase worldwide. Mycobacterium tuberculosis (Mtb) , the bacteria that causes TB, grows primarily within macrophages. TB treatment includes 3-4 antibiotics taken together for 4-9 months that can lead to frequent side-effects and often has poor patient adherence. The use of drug delivery systems targeting therapeutics directly to infected macrophages could reduce the dose needed for treatment, potentially eliminating side effects and improving compliance. We developed folate-conjugated liposomes encapsulating rifampicin, a first-line anti-Mtb drug, to examine whether macrophage targeting could improve treatment of intracellular Mtb. Flow cytometry and confocal microscopy demonstrate that folate functionalized liposomes enhance macrophage targeting as compared to non-targeted liposomes. Finally, we demonstrate that folate-conjugated liposomes do not increase toxicity and can be used to improve clearance of intracellular Mtb. These findings establish folate-conjugated liposomes as a powerful new tool with the potential to help in the fight against tuberculosis.