Wits Scientists Develop Breakthrough Nanomedicine to Combat Drug-Resistant TB in Heart and Lungs
核心洞察
Scientists at Wits University's Advanced Drug Delivery Platform have developed innovative nanosystems to deliver tuberculosis (搜索) drugs directly to infection sites in both the lungs and heart, bypassing traditional barriers that limit treatment effectiveness.
The inhalable nanosystem can carry all four standard TB drugs in a single formulation and release them precisely at lung infection sites, potentially shortening treatment time and improving patient adherence.
A separate breakthrough involves nanoparticles that can penetrate the heart's protective membrane to deliver bedaquiline directly to treat TB pericarditis (搜索), one of the most lethal forms of tuberculosis (搜索) with the highest mortality rates.
Scientists at the Wits Advanced Drug Delivery Platform (搜索) (WADDP) have developed two groundbreaking nanosystems that could revolutionize tuberculosis (搜索) treatment by delivering drugs directly to infection sites that conventional therapies cannot reach. The innovations target both pulmonary TB and the deadly cardiac form known as TB pericarditis (搜索), addressing critical gaps in current treatment approaches.
Inhalable Nanosystem Targets Lung Infections
Postdoctoral researcher Dr. Lindokuhle Ngema is developing an inhalable nanosystem designed to transport TB medicines directly into the lungs, where Mycobacterium tuberculosis (搜索) hides and thrives in pockets that oral drugs cannot reach. The nanocarrier can hold all four standard TB drugs—rifampicin, isoniazid, ethambutol, and pyrazinamide—in a single formulation and release them precisely at the infection site.
"TB is clever," says Ngema. "It hides in lung pockets where oral drugs can't reach. Our system is designed to be smarter and to go exactly where it's needed."
The system is engineered to bypass the liver and bloodstream, reducing drug loss while increasing local concentration in the lungs. By delivering medicine directly into the respiratory tract, from the nose and bronchi to the alveoli, inhaled treatment bypasses the body's barriers and concentrates the drug where it is needed most.
Working with the Nuclear Medicine Research Institute (搜索) (NuMeRI), the team will use nuclear imaging to track how the nanoparticles move through the lung in real time, confirming whether the drug reaches the "hidden" TB pockets that conventional therapy misses.
Breaking Through the Heart's Protective Barrier
In a separate breakthrough, WADDP scientists have developed a nanosystem to treat TB pericarditis (搜索), which has one of the highest mortality rates of all TB forms because antibiotics cannot reach the site of infection. The system can breach the heart's protective membrane, a barrier that standard antibiotics cannot penetrate to be therapeutic.
The team designed a 100-200 nm nanoparticle made from two natural polymers, COS and mannan. COS helps the particle slip through the tight cell layers of the pericardium, while mannan guides it directly to macrophages (搜索)—immune cells where tuberculosis (搜索) bacteria hide and multiply. Inside this particle, bedaquiline, a first-line treatment for drug-resistant TB, is safely packaged and released slowly once it enters the cell.
"By engineering a nanosystem that crosses the pericardium and delivers bedaquiline directly to infected immune cells, we are opening a pathway to treat a condition that has long been considered almost untreatable," says Professor Yahya Choonara, WADDP's Director.
In laboratory studies using both porcine and human pericardium, the nanoparticle worked consistently across tissue types. The particles moved bedaquiline steadily across the membrane without damaging or weakening the tissue, an important sign for potential clinical translation.
Addressing Global Health Crisis
These innovations come at a critical moment as antimicrobial resistance (AMR) increases rapidly worldwide. AMR kills more people every year than HIV/AIDS and malaria combined, with nearly five million deaths linked to drug-resistant infections in 2019. The World Bank's global economic modeling suggests the world could face financial losses equivalent to repeating the 2008 global financial crisis annually by 2050 if no action is taken.
TB remains a major global killer, causing about 10 million new infections and 1.8 million deaths each year. In South Africa alone, TB claimed more than 56,000 lives in 2023. The World Health Organization's End TB Strategy calls for 80 percent fewer new cases and 90 percent fewer deaths by 2030.
"If we want to end TB, we must also address the limitations of one-size-fits-all drug delivery," says Choonara. "Precision nanomedicine like this allows us to treat smarter, faster and with greater impact, which is exactly what the WHO's End TB Strategy is calling for."
Overcoming Treatment Challenges
Standard TB treatment involves taking four key anti-TB drugs over six months, creating challenges with adherence. Side effects include nausea, liver damage, and neuropathy, which may cause patients to stop taking their medicine. This allows TB to evolve into multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms.
The WADDP team believes that inhalation therapy could provide a breakthrough by shortening treatment time, improving adherence, and helping limit the rise of drug resistance. The biocompatible carriers are engineered at the molecular level to be non-toxic, with the body not recognizing them as foreign or dangerous.
Expanding Applications
The team has also been developing polydopamine (PDA) nanoparticles designed to penetrate hard, scar-like structures known as granulomas where TB bacteria hide. These particles can carry multiple types of payloads simultaneously, including imaging agents and immune-boosting molecules, potentially helping doctors both see and treat TB more precisely while reducing toxicity.
"If bedaquiline can be delivered intrapericardially in sustained, low-frequency doses, this could become a blueprint for treating other hard-to-reach infections, from lymphatic TB to central nervous system involvement," says Choonara.
The research addresses diseases and anatomical challenges that disproportionately affect low- and middle-income countries. TB pericarditis (搜索) has a high burden in southern Africa due to HIV co-infection and late diagnosis. Conventional regimens fail not because the drugs lack potency, but because they cannot arrive at relevant tissues at therapeutic concentrations.
For Ngema, this research carries personal significance. "TB has taken too many lives for too long," he says. "If we can make treatment easier, faster and smarter, then we're not just improving outcomes, but restoring hope."