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

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.