(675a) Multi-Drug Loaded BIOMOFs Clear Mycobacterium Tuberculosis Infection
AIChE Annual Meeting
Thursday, November 14, 2019 - 12:30pm to 12:48pm
RESULTS â Herein, we put forth a new strategy, which designs and selects drug delivery materials based on the properties of (even multiple, simultaneously) encapsulated drugs, instead of attempting to accommodate these drugs into conventional delivery systems. Specifically, through an in-silico screening process of 5109 MOFs using grand canonical Monte Carlo screening techniques, a customized MOF (referred as BIO-MOF-100) was selected and experimentally verified to be biologically stable, and capable of loading 3 anti-Tb drugs Rifampicin+Isoniazid+Pyrazinamide at 10%+28%+23% wt/wt (total >50% by weight, 2-orders of magnitude higher than is possible with any degradable polymer matrix to our knowledge).
BIO-MOF-100 were also able to release these drugs in a sustained manner. Notably, the customized BIO-MOF-100 delivery system cleared naturally Pyrazinamide-resistant Bacillus Calmette-Guérin (BCG) vaccine strain,
reduced growth of virulent H37Rv Mtb infection in macaque bronchoalveolar (BAL) macrophages 10-100-fold compared to soluble drugs in vitro and was also capable of targeting the lungs of mice. These data suggest that the methodology of identifying-synthesizing materials can be used to generate solutions for challenging applications such as simultaneous delivery of multiple, small hydrophilic and hydrophobic molecules in the same molecular framework.
CONCLUSION - In summary, a methodology capable of screening thousands of potential molecular structures that can load high levels of multiple anti-TB drugs has been presented. Using this process, a new MOF structure (referred to here as BIO-MOF-100) was selected, experimentally synthesized, and deterred to load all three anti-TB small molecules at two orders of magnitude higher than has been seen to date. These new materials were able to eliminate BCG infection and prevent H37Rv infection in macrophages effectively.