In silico identification and synthesis of a multi-drug loaded MOF for treating tuberculosis.

Conventional drug delivery systems have been applied to a myriad of active ingredients but may be difficult to tailor for a given drug. Herein, we put forth a new strategy, which designs and selects the drug delivery material by considering the properties of encapsulated drugs (even multiple drugs, simultaneously). Specifically, through an in-silico screening process of 5109 MOFs using grand canonical Monte Carlo simulations, a customized MOF (referred as BIO-MOF-100) was selected and experimentally verified to be biologically stable, and capable of loading 3 anti-Tuberculosis drugs Rifampicin+Isoniazid+Pyrazinamide at 10% + 28% + 23% wt/wt (total > 50% by weight). Notably, the customized BIO-MOF-100 delivery system cleared naturally Pyrazinamide-resistant Bacillus Calmette-Guérin, reduced growth of virulent Erdman infection in macaque macrophages 10-100-fold compared to soluble drugs in vitro and was also significantly reduced Erdman growth in 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.

Metal-Organic Frameworks for Drug Delivery: A Design Perspective.

The use of metal-organic frameworks (MOFs) in biomedical applications has greatly expanded over the past decade due to the precision tunability, high surface areas, and high loading capacities of MOFs. Specifically, MOFs are being explored for a wide variety of drug delivery applications. Initially, MOFs were used for delivery of small-molecule pharmaceuticals; however, more recent work has focused on macromolecular cargos, such as proteins and nucleic acids. Here, we review the historical application of MOFs for drug delivery, with a specific focus on the available options for designing MOFs for specific drug delivery applications. These options include choices of MOF structure, synthetic method, and drug loading. Further considerations include tuning, modifications, biocompatibility, cellular targeting, and uptake. Altogether, this Review aims to guide MOF design for novel biomedical applications.

Synthesis and characterization of CaSr-Metal Organic Frameworks for biodegradable orthopedic applications.

Metal-organic frameworks (MOFs) formed from metals and organic ligands, are crystalline materials that are degradable in aqueous medium, and capable of releasing Ca and Sr ions. In this manuscript, the ability of MOFs to degrade and release osteogenic Ca and Sr ions was investigated. MOFs were generated by choosing osteoinductive Ca and Sr metals, and an organic ligand 1,3,5 tricarboxylicbenzene (H3BTC) as a linker. These MOFs were able to induce in vitro biomineralization from pre-osteoblastic MC3T3 cells and human mesenchymal stem cells (hMSCs). Moreover, these MOFs (when loaded with dimethyloxalylglycine (DMOG)) induced vascular endothelial production from hMSCs. qRT-PCR analysis performed on hMSCs (isolated from femoral heads of patients undergoing joint arthroplasty) treated with MOFs crystals suggested that the CaSr-MOFs by themselves can upregulate osteogenic genes in hMSCs, which is the first time to our knowledge that this has been observed from MOFs.