(509a) Ultrahigh and Multiple Anti-Tuberculosis Drugs Loaded BioMOFs Clear Mycobacterium Tuberculosis Infection in Macrophages

Authors: 
Acharya, A. P., University of Pittsburgh
Greene, A., University of Pittsburgh
Little, S., University of Pittsburgh
Sezginel, K. B., University of Pittsburgh
Wilmer, C. E., University of Pittsburgh
Tuberculosis (TB) causes ~2 million deaths/year, and the clearance of mycobacterium tuberculosis (M.tb) remains difficult due to the requirement of multiple anti-TB drugs intracellularly (site of infection) to be effective. Herein, for the first time a systematic in silico and experimental metal-organic framework (MOF) selection (from 5109 MOFs) for highest %drug loading is utilized to select a MOF that is capable of delivering 3 anti-TB drugs (Rifampicin-RFP, Isoniazid-INH, Pyrazinamide-PYZ) simultaneously and intracellularly. Using this methodology, SAPBIW MOF was selected, which could load RFP+INH+PYZ at 10%+28%+23% wt/wt in the same crystal. Notably, SAPBIW delivering anti-TB drugs cleared non-virulent PYZ-resistant mycobacterium bovis and virulent H37Rv M.tb infection in macaque macrophages 10-100-fold more effectively than soluble drugs in vitro, and could be delivered in deep-lung-tissue of mice. These data suggest that MOFs are excellent delivery vehicle for small-hydrophilic-molecules (difficult to encapsulate in traditional polymers) and can be effective for TB treatment.