Abstract |
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.
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Authors | Abhinav P Acharya, Kutay B Sezginel, Hannah P Gideon, Ashlee C Greene, Harrison D Lawson, Sahil Inamdar, Ying Tang, Amy J Fraser, Kush V Patel, Chong Liu, Nathaniel L Rosi, Stephen Y Chan, JoAnne L Flynn, Christopher E Wilmer, Steven R Little |
Journal | Journal of controlled release : official journal of the Controlled Release Society
(J Control Release)
Vol. 352
Pg. 242-255
(12 2022)
ISSN: 1873-4995 [Electronic] Netherlands |
PMID | 36273529
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2022 Elsevier B.V. All rights reserved. |
Chemical References |
- Pyrazinamide
- Pharmaceutical Preparations
- Antitubercular Agents
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Topics |
- Mice
- Animals
- Pyrazinamide
- Pharmaceutical Preparations
- Drug Delivery Systems
- Antitubercular Agents
(therapeutic use)
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