Researchers at the University at Buffalo’s Jacobs School of Medicine and Biomedical Sciences have developed an inhalable treatment for tuberculosis (TB) that utilizes nanoparticles to deliver medication directly to the lungs, potentially reducing the lengthy and often debilitating treatment regimen currently required for the disease.
The findings, published in the journal Antimicrobial Agents and Chemotherapy, detail a biocompatible nanoparticle system encapsulating rifampin, a crucial drug in TB treatment. Jessica L. Reynolds, PhD, associate professor of medicine at the Jacobs School, led the research.
“TB is still one of the world’s deadliest infectious diseases, even though it can be cured,” Reynolds said. “Treatment takes many months and involves multiple drugs that can cause serious side effects. As of this, many patients struggle to finish treatment, which leads to treatment failure and drug-resistant TB.”
Current oral rifampin treatment can cause liver damage and often fails to deliver sufficient drug concentrations directly to the lungs, where the TB bacteria reside. The University at Buffalo team addressed these challenges by packaging rifampin within nanoparticles designed for inhalation. These particles are engineered with a biodegradable core, an outer coating to enhance uptake by macrophages – immune cells where TB bacteria hide – and a natural molecule to further boost immune activity, according to Hilliard L. Kutscher, research assistant professor of medicine and first author of 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,” Kutscher explained. “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 research team tested the inhalable nanoparticles in two different mouse models of TB, including one that closely mimics the severe lung damage seen in human cases. Results indicated that weekly administration of the inhaled nanoparticles was as effective as, or even more effective than, daily oral rifampin in reducing the presence of Mycobacterium tuberculosis.
“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 noted.
All studies involving Mycobacterium tuberculosis were conducted in a certified Biosafety Level 3 (BSL-3) facility, adhering to stringent federal, state, and institutional safety regulations.
Reynolds highlighted the potential for simplifying TB therapy with this approach. “Reducing treatment frequency could improve adherence, lower side effects and make TB care more accessible worldwide,” she said. “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.”
The researchers are now investigating how the nanoparticle system can be combined with other standard TB antibiotics to support combination therapy, the current cornerstone of TB treatment.
Patrick O. Kenney, clinical assistant professor of pediatrics and a coauthor on the study, pointed to potential benefits beyond tuberculosis. Rifampin is also used to treat lung 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 noted that targeted lung delivery could resolve a significant drug interaction issue. Oral rifampin activates liver enzymes that 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 harmful interactions, expanding rifampin’s utility in treating a wider range of pulmonary mycobacterial diseases.
The research was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
