UB researchers develop new inhalable treatment for TB: Study

Researchers at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo have developed a new inhalable form of tuberculosis (TB) treatment that could significantly reduce the burden of current therapy.

The study’s findings were published online Jan. 14 in the journal Antimicrobial Agents and Chemotherapy. Jessica L. Reynolds, PhD, associate professor of medicine in the Jacobs School, is senior author on the paper, titled “Repeated Pulmonary Dosing of β-Glucan-Chitosan-PLGA Nanoparticles Controls Mycobacterium Tuberculosis in Mice.”

The paper details the development of an inhalable, immunomodulating, biocompatible nanoparticle system encapsulating rifampin, one of the most important TB drugs.

“TB is still one of the world’s deadliest infectious diseases, even though it can be cured. Treatment takes many months and involves multiple drugs that can cause serious side effects,” Reynolds says. “Because of this, many patients struggle to finish treatment, which leads to treatment failure and drug-resistant TB.”

Potential for lower side effects, fewer dosages

Rifampin works well but has two major drawbacks when taken orally: It can damage the liver and not enough of the drug reaches the lungs, where TB bacteria live, Reynolds notes.

To address this, the researchers developed a new way to deliver rifampin directly to the lungs by inhalation instead of pills by packaging the drug into nanoparticles designed to be breathed in.

The nanoparticles have a biodegradable core that holds rifampin, an outer coating that helps them stick to macrophages and a natural molecule on the surface that both improves uptake by immune cells and boosts immune activity, says Hilliard L. Kutscher, PhD, research assistant professor of medicine, and first author on the study.

“These particles are specially built to go straight to the lungs and be taken up by lung immune cells called macrophages, which are where TB bacteria hide,” he adds. “They are designed to slowly release rifampin over time, to stimulate the immune system to better fight TB and to reduce drug exposure to the rest of the body, lowering side effects.”

Because the drug stays in the lungs longer using this form of delivery, treatment might only be needed once a week instead of every day, Kutscher suggests.

Drug delivered more effectively to lungs

In the study, the researchers used two different mouse models of TB (one that reflects general TB lung infection, and a second, more severe model that closely mimics human TB lung damage and is harder to treat) to test whether once-weekly inhaled nanoparticles work as well as — or better than — daily oral rifampin in reducing mycobacterium tuberculosis.

“Using both models makes the results more reliable and relevant to human disease,” Reynolds says.

The study found that inhaled nanoparticle treatment delivered rifampin much more effectively to the lungs.

“Compared to taking rifampin by mouth every day, the inhaled nanoparticles kept higher levels of the drug in the lungs for much longer — up to a week after a single dose,” Reynolds notes.

All studies involving Mycobacterium tuberculosis were conducted in a certified Biosafety Level 3 (BSL-3) facility, the standard laboratory environment required for TB research nationwide. These facilities operate under established federal, state and institutional regulations and include controlled access, specialized ventilation, sterilization and other validated safety procedures.

“The work highlights the potential of long-acting inhaled medicines to simplify TB therapy,” Reynolds says.

“Reducing treatment frequency could improve adherence, lower side effects and make TB care more accessible worldwide,” she says. “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.”

She adds that the next phase of this research will focus on how the nanoparticle can be integrated with other standard TB antibiotics to support combination therapy, the cornerstone of TB treatment of disease.

Potential benefits extend beyond TB

Patrick O. Kenney, MD, clinical assistant professor of pediatrics and co-author on the study, says the potential public health benefits of the research go beyond tuberculosis.

“Rifampin is not just a TB drug; it is also a key medication for other serious lung infections caused by non-tuberculous mycobacteria, such as Mycobacterium kansasii and Mycobacterium xenopi, which are increasingly recognized in the U.S.,” Kenney says. “These infections often affect people with chronic lung disease and can be difficult to treat.”

Kenney says targeted lung delivery could also potentially solve a long-standing drug interaction problem.

“One major limitation of rifampin is that when taken orally, it strongly activates liver enzymes and this reduces the effectiveness of other important antibiotics, such as azithromycin and clarithromycin, which are cornerstones of therapy for Mycobacterium avium/intracellulare complex (MAC) lung disease,” he says. “Because of this interaction, rifampin is often avoided, even when it could otherwise help.”

However, by delivering rifampin directly to the lungs instead of the whole body, this approach could achieve high drug levels at the site of the infection, minimize drug levels in the bloodstream and potentially reduce harmful drug-drug interactions, Kenney notes.

“That opens the door to using rifampin more effectively in a broader range of pulmonary mycobacterial diseases — not just TB,” he says.

Reference:

Kutscher HL, Tamblin M, Smith E, Shah A, Kenney PO, Reynolds JL. 2026. Repeated pulmonary dosing of β-glucan-chitosan-PLGA nanoparticles controls Mycobacterium tuberculosis in mice. Antimicrob Agents Chemother 70:e01480-25. https://doi.org/10.1128/aac.01480-25