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Lung Delivery of Antibiotics Using Metal-Organic Frameworks Shows Promise Against Respiratory Infections
Researchers from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, MEPhI, the Kurchatov Institute, and Uppsala University have developed a novel nanoparticle system for the effective delivery of rifampicin to the lungs. Using metal-organic frameworks (MOFs) with a MIL-101(Cr) structure, the team achieved high antibiotic loading and sustained release, offering a potential breakthrough in treating bacterial lung infections, including tuberculosis. The study was published in the journal Biomedical Materials.
Respiratory infections such as pneumonia, bronchitis, and tuberculosis remain leading causes of mortality worldwide. Conventional antibiotic therapies often suffer from poor targeting, leading to low drug concentrations in the lungs, systemic side effects, and increased risk of antibiotic resistance. The new MOF-based delivery system aims to overcome these limitations by ensuring precise, sustained antibiotic release directly at the site of infection.
The researchers synthesized two types of MOF nanoparticles: MIL-101(Cr) and its amino-modified counterpart, NH2-MIL-101(Cr). Both were loaded with a first-line tuberculosis drug rifampicin and coated with polyacrylic acid to improve stability in physiological conditions. The particles exhibited exceptionally high drug loading, up to 127% by weight, and released the antibiotic in a controlled manner over 48 hours.
In animal studies, the amino-modified MOFs showed a strong tropism for lung tissue, accumulating at levels nearly 300% per gram of tissue, more than 10 times higher than in other organs. This targeted accumulation is attributed to the interaction of positively charged amino groups with lung capillary endothelium.
The lead author, Aziz Mirkasymov, noted: “Our system allows for a sustained release of the drug at the site of infection, maintaining sufficient concentrations over much longer periods, which is crucial for effective therapy of chronic bacterial infections.”
The rifampicin-loaded MOFs demonstrated significant antibacterial activity against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, reducing bacterial viability even at low concentrations. The particles also showed good biocompatibility in cellular and hemolysis assays, indicating potential for safe systemic administration.
This approach could reduce the frequency of drug administration, minimize side effects, and improve patient adherence to treatment regimens. The study opens new avenues for using MOFs in pulmonary drug delivery and infectious disease therapy.
The work was supported by the Russian Science Foundation, Agreement No. 25-24-00299.
january 27