University at Buffalo Researchers Develop Inhalable Nanoparticle System for Tuberculosis Treatment
核心洞察
University at Buffalo researchers have developed an inhalable nanoparticle system that delivers rifampin directly to the lungs, potentially reducing tuberculosis (搜索) treatment from daily to weekly dosing.
The biocompatible nanoparticles maintained higher drug levels in the lungs for up to a week after a single dose compared to daily oral rifampin in mouse models.
The targeted delivery approach could reduce liver toxicity and drug interactions while improving treatment adherence for tuberculosis (搜索) and other mycobacterial lung infections.
Researchers at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo have developed a novel inhalable nanoparticle system for tuberculosis (搜索) treatment that could transform how patients receive therapy for one of the world's deadliest infectious diseases. The breakthrough, published January 14 in Antimicrobial Agents and Chemotherapy, demonstrates the potential to reduce treatment frequency from daily to weekly dosing while improving drug delivery to infected lung tissue.
Addressing Critical Treatment Challenges
"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," said Jessica L. Reynolds, PhD, associate professor of medicine and senior author of the study. "Because of this, many patients struggle to finish treatment, which leads to treatment failure and drug-resistant TB."
The research team focused on rifampin, one of the most important tuberculosis (搜索) drugs, which faces significant limitations when administered orally. Reynolds noted that rifampin "can damage the liver and not enough of the drug reaches the lungs, where TB bacteria live" when taken as pills.
Innovative Nanoparticle Design
The researchers developed a sophisticated nanoparticle system with multiple therapeutic components. According to first author Hilliard L. Kutscher, PhD, research assistant professor of medicine, the nanoparticles feature "a biodegradable core that holds rifampin, an outer coating that helps them stick to macrophages (搜索) and a natural molecule on the surface that both improves uptake by immune cells and boosts immune activity."
"These particles are specially built to go straight to the lungs and be taken up by lung immune cells called macrophages (搜索), 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."
Superior Drug Delivery Performance
The research team tested their approach using two different mouse models of tuberculosis (搜索) in a certified Biosafety Level 3 facility. One model reflected general TB lung infection, while a second, more severe model closely mimicked human TB lung damage and proved harder to treat.
"Using both models makes the results more reliable and relevant to human disease," Reynolds said. The study demonstrated that the inhaled nanoparticle treatment delivered rifampin much more effectively to the lungs compared to oral administration.
"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. This extended drug retention suggests that treatment frequency could be reduced to once weekly instead of daily dosing.
Broader Therapeutic Applications
The potential benefits of this delivery system extend beyond tuberculosis (搜索) treatment. Patrick O. Kenney, MD, clinical assistant professor of pediatrics and co-author, highlighted the broader implications for mycobacterial lung infections.
"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 (搜索) and Mycobacterium xenopi (搜索), which are increasingly recognized in the U.S.," Kenney said. "These infections often affect people with chronic lung disease and can be difficult to treat."
The targeted lung delivery approach could also address a significant drug interaction problem. Kenney explained that when rifampin is 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 (搜索) (MAC) lung disease."
By delivering rifampin directly to the lungs, the 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," according to Kenney. "That opens the door to using rifampin more effectively in a broader range of pulmonary mycobacterial diseases — not just TB."
Clinical Implications and Future Development
The research addresses a critical public health challenge, as treatment compliance issues contribute significantly to the development of drug-resistant tuberculosis (搜索). "Reducing treatment frequency could improve adherence, lower side effects and make TB care more accessible worldwide," Reynolds said.
The next phase of research will focus on integrating the nanoparticle system with other standard TB antibiotics to support combination therapy, which Reynolds described as "the cornerstone of TB treatment."
The study was conducted by a multidisciplinary team including undergraduate students Arnav Shah and Evon Smith, along with research technician Maria Tamblin. The research received funding from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.