New Inhalable Treatment for TB Lowers Side Effects

Tuberculosis (TB) remains one of the world’s deadliest infectious diseases, despite being curable. Treatment requires months of multiple drugs that can cause serious side effects, leading many patients to discontinue therapy and increasing the risk of treatment failure and drug resistance. Rifampin, a key TB drug, can damage the liver when taken orally and often does not reach sufficient levels in the lungs, where the bacteria reside. Researchers have now developed an inhalable version designed to deliver the drug directly to lung immune cells while reducing systemic exposure.

Researchers at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo (Buffalo, NY, USA) have developed an immunomodulating, biocompatible nanoparticle system encapsulating rifampin. The particles contain a biodegradable core that holds the drug, an outer coating that enhances attachment to macrophages, and a surface molecule that improves immune cell uptake while boosting immune activity.

Designed for inhalation, the nanoparticles are taken up by lung macrophages, where TB bacteria hide. The system slowly releases rifampin over time, maintaining higher concentrations in the lungs while reducing drug exposure elsewhere in the body. Researchers tested the inhaled nanoparticles in two mouse models of TB, including a severe model that closely mimics human lung damage. The once-weekly inhaled formulation was compared with daily oral rifampin.

The findings, published in Antimicrobial Agents and Chemotherapy, show that the inhaled treatment delivered significantly higher lung concentrations of rifampin and maintained therapeutic levels for up to a week after a single dose. The nanoparticle therapy effectively controlled Mycobacterium tuberculosis infection, demonstrating improved drug delivery compared to oral dosing.

Because the inhaled formulation prolongs drug retention in the lungs, treatment frequency could potentially be reduced from daily dosing to once weekly, improving adherence and lowering side effects. The researchers are now investigating how the nanoparticle platform can be combined with other standard TB antibiotics to support multi-drug therapy. In addition to TB, this targeted lung delivery approach may benefit patients with non-tuberculous mycobacterial infections and could reduce drug-drug interactions associated with oral rifampin use.

“The work highlights the potential of long-acting inhaled medicines to simplify TB therapy,” said Associate Professor Jessica L. Reynolds, PhD, senior author on the paper. “These findings support continued development of inhalable, long-acting TB therapies as a promising strategy to improve treatment outcomes and reduce the global impact of tuberculosis.”

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