Inhalable TB Treatment Could Replace Daily Pills with Once-Weekly Doses

Tuberculosis is still one of the world's deadliest infectious diseases, killing over 1.3 million people annually. Even though it can be cured, treatment is brutal: many months of daily pills with serious side effects, including liver damage. Roughly one in four patients struggles to finish treatment, leading to drug-resistant TB that's even harder to cure.

But researchers at the University at Buffalo have developed something that could transform TB care: an inhalable treatment that delivers medication directly to the lungs, where TB bacteria hide, potentially reducing the regimen from daily oral pills to once-weekly inhaled doses.

The study's findings, published February 13, 2026, in the journal Antimicrobial Agents and Chemotherapy, could mark the beginning of the end for one of TB treatment's biggest challenges: getting patients to stick with therapy long enough to be cured.

The Problem with Current TB Treatment

"TB is still one of the world's deadliest infectious diseases, even though it can be cured," says Dr. Jessica L. Reynolds, associate professor of medicine at the University at Buffalo's Jacobs School of Medicine and Biomedical Sciences and senior author on the study.

"Treatment takes many months and involves multiple drugs that can cause serious side effects. Because of this, many patients struggle to finish treatment, which leads to treatment failure and drug-resistant TB."

Rifampin, one of the most important TB drugs, has two major drawbacks when taken orally:

• It can damage the liver (hepatotoxicity is a serious concern)
• Not enough reaches the lungs, where TB bacteria actually live and multiply inside immune cells called macrophages

Most of the oral dose gets absorbed into the bloodstream and distributed throughout the body — causing systemic side effects while delivering sub-optimal concentrations to the actual site of infection.

The Breakthrough: Nanoparticles That Go Straight to the Target

To solve this problem, the research team developed a nanoparticle system that packages rifampin into tiny particles designed to be breathed in, like using an asthma inhaler or nebulizer.

These aren't ordinary nanoparticles. They're engineered with three key features:

1. A biodegradable core that holds rifampin: The drug is safely encapsulated in a material that breaks down naturally in the body.

2. An outer coating that targets macrophages: The particles are designed to stick to the lung immune cells where TB bacteria hide — delivering the drug exactly where it's needed.

3. A natural molecule that boosts immune activity: The surface includes a component that not only helps immune cells take up the nanoparticles but also stimulates the immune system to better fight TB.

"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," explains Hilliard L. Kutscher, research assistant professor of medicine and first author on the study.

"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."

The Results: One Dose Lasts a Full Week

The team tested their inhalable nanoparticles in two different mouse models of TB — one representing general lung infection, and a second, more severe model that closely mimics the lung damage seen in human TB patients.

"Using both models makes the results more reliable and relevant to human disease," Reynolds notes.

The findings were striking:

Inhaled nanoparticles delivered rifampin MUCH more effectively to the lungs. Compared to taking rifampin orally 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.

This means patients could potentially inhale their TB medication once a week instead of swallowing pills every single day.

Why This Changes Everything

The potential benefits of this breakthrough extend far beyond convenience:

Better adherence: Taking medication once a week is dramatically easier than daily pills for months on end. Better adherence means more cures and less drug-resistant TB.

Fewer side effects: Because the drug goes straight to the lungs instead of circulating through the whole body, systemic side effects (especially liver damage) could be dramatically reduced.

Higher drug concentrations where they matter: TB bacteria hide in lung macrophages. These nanoparticles deliver high drug levels exactly where the bacteria live, potentially making treatment more effective.

Immune system boost: The nanoparticles don't just deliver the drug — they also stimulate the immune system to fight TB more effectively.

"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."

Beyond Tuberculosis

The implications reach beyond TB. Dr. Patrick O. Kenney, clinical assistant professor of pediatrics and coauthor on the study, points out that rifampin is also crucial for treating non-tuberculous mycobacterial (NTM) infections — serious lung infections caused by bacteria like Mycobacterium kansasii, M. xenopi, and Mycobacterium avium/intracellulare complex (MAC).

These infections often affect people with chronic lung diseases and are increasingly common in the US.

There's also a major drug interaction problem: when rifampin is taken orally, it strongly activates liver enzymes, which reduces the effectiveness of other critical antibiotics like azithromycin and clarithromycin — cornerstones of MAC treatment. Because of this interaction, rifampin is often avoided even when it could help.

"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 explains.

"That opens the door to using rifampin more effectively in a broader range of pulmonary mycobacterial diseases — not just TB."

What's Next?

The research was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, signaling strong institutional support for moving this forward.

Reynolds says the next phase will focus on integrating the nanoparticle system with other standard TB antibiotics to support combination therapy — the cornerstone of effective TB treatment.

All studies involving Mycobacterium tuberculosis were conducted in a certified Biosafety Level 3 (BSL-3) facility under strict federal, state, and institutional safety protocols, ensuring rigorous scientific standards.

A Global Health Game-Changer

Tuberculosis kills more people than any other infectious disease except COVID-19. In 2022, 10.6 million people fell ill with TB and 1.3 million died. The disease disproportionately affects low- and middle-income countries where access to daily medical care is limited.

An inhaled, once-weekly treatment that's easier to take, has fewer side effects, and works better could save hundreds of thousands of lives annually.

And because the nanoparticle system targets the lungs directly, it could also help treat other serious lung infections that currently require daily pills for months or years.

The Takeaway

TB treatment hasn't fundamentally changed in decades. It's still a grueling, months-long ordeal with harsh side effects that many patients can't complete.

This inhalable nanoparticle system could finally modernize TB care: once-weekly inhaled doses that deliver medication exactly where it's needed, boost the immune system, and minimize side effects.

It's early-stage research, but the results are promising enough to move toward combination therapy trials — the next step before human testing.

For the millions of people battling TB worldwide, that single weekly inhale could mean the difference between treatment failure and a cure.

Source: University at Buffalo, Antimicrobial Agents and Chemotherapy, February 13, 2026