Inhalable Tuberculosis Treatment: Nanoparticles Show Promise for Faster, Fewer Doses

New Inhalable Treatment Shows Promise for Tuberculosis

Researchers have developed a novel inhalable treatment for tuberculosis (TB) that could significantly improve current therapy and address challenges with patient adherence and drug side effects. The findings, published in Antimicrobial Agents and Chemotherapy, detail a nanoparticle system designed to deliver rifampin, a crucial TB medication, directly to the lungs.

TB remains a leading cause of infectious disease mortality worldwide, despite being curable. Current treatment regimens are lengthy, often spanning months, and involve multiple drugs that can cause substantial side effects. These factors frequently lead to patients struggling to complete their treatment, resulting in treatment failure and the emergence of drug-resistant strains.

“TB is still one of the world’s deadliest infectious diseases, even though it can be cured,” explains Jessica L. Reynolds, associate professor of medicine at the University at Buffalo and senior author of the study. “Treatment takes many months and involves multiple drugs that can cause serious side effects.”

Addressing Limitations of Oral Rifampin

While rifampin is an effective TB drug, it presents two key drawbacks when administered orally. It can cause liver damage, and a significant portion of the drug doesn’t reach the lungs, the primary site of TB infection. The researchers aimed to overcome these limitations by developing a method for direct lung delivery via inhalation.

The newly developed nanoparticles consist of a biodegradable core containing rifampin, an outer coating that promotes adhesion to macrophages (immune cells), and a natural molecule on the surface that enhances uptake by immune cells and boosts immune activity. Hilliard L. Kutscher, research assistant professor of medicine and first author of the study, describes the particles as “specially built to go straight to the lungs and be taken up by lung immune cells called macrophages, which are where TB bacteria hide.”

The design allows for a slow, sustained release of rifampin, stimulating the immune system to fight the infection while minimizing drug exposure to other parts of the body and potentially reducing side effects.

Promising Results in Mouse Models

The efficacy of the inhalable nanoparticle treatment was evaluated in two different mouse models of TB. One model reflected a typical lung infection, while the other mimicked the more severe lung damage seen in human TB cases, which is often harder to treat. The study investigated whether weekly administration of the inhaled nanoparticles was as effective as, or even superior to, daily oral rifampin in reducing the bacterial load of Mycobacterium tuberculosis.

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

The results demonstrated that the inhaled nanoparticle treatment delivered rifampin more effectively to the lungs. Compared to daily oral administration, the nanoparticles maintained higher drug concentrations in the lungs for an extended period—up to a week after a single dose.

“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 explains.

All studies involving Mycobacterium tuberculosis were conducted in a certified Biosafety Level 3 (BSL-3) facility, adhering to stringent safety protocols, and regulations.

Potential for Simplified Treatment and Broader Applications

The researchers suggest that this delivery method could potentially reduce the frequency of treatment from daily to weekly, which could significantly improve patient adherence and accessibility to care, particularly in resource-limited settings.

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

The team plans to further investigate the integration of these nanoparticles with other standard TB antibiotics to support combination therapy, the current cornerstone of TB treatment.

Beyond TB, the research has implications for other serious lung infections. Patrick O. Kenney, clinical assistant professor of pediatrics and coauthor of the study, points out that rifampin is also used to treat infections caused by non-tuberculous mycobacteria, such as Mycobacterium kansasii and Mycobacterium xenopi, which are increasingly prevalent in the United States, particularly among individuals with chronic lung disease.

Kenney also highlights the potential to address drug interactions. Oral rifampin activates liver enzymes that can reduce the effectiveness of other antibiotics, like azithromycin and clarithromycin, used to treat Mycobacterium avium/intracellulare complex (MAC) lung disease. By delivering rifampin directly to the lungs, the researchers believe they can minimize systemic exposure and potentially avoid these interactions.

“Because of this interaction, rifampin is often avoided, even when it could otherwise help,” Kenney says. “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.”

This research was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.