Breaking the heart’s barrier to solve drug-resistant TB
- Wits University
African scientists develop nanoscale drug delivery system to treat pericarditis, a drug-resistant and lethal tuberculosis (TB).
The scientists’ system can breach the heart’s protective membrane, a barrier that standard antibiotics cannot penetrate to be therapeutic.
This breakthrough from the Wits Advanced Drug Delivery Platform (WADDP) comes at a critical moment: As more infections become resistant to multiple antibiotics, antimicrobial resistance (AMR) is increasing rapidly.
WADDP’s strategy is to build precision nanoscale drug-delivery systems that enable existing medicines to reach the correct tissues, stay there longer, act more potently, and avoid toxicity.
TB pericarditis has one of the highest mortality rates of all TB forms because antibiotics cannot reach the site of infection.
“By engineering a nanosystem that crosses the pericardium and delivers bedaquiline [a first-line treatment for drug-resistant and extensively drug-resistant TB] 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.
Bedaquiline is oily and usually hard to deliver to protected sites like the heart. Getting it through this otherwise impenetrable membrane is a significant step forward. It means doctors could one day deliver the drug directly into the pericardial space, achieving much higher local concentrations, fewer side effects, and potentially far fewer doses.
AMR kills more people every year than HIV/AIDS and malaria combined. Nearly five million deaths were linked to drug-resistant infections in 2019, and the World Bank’s global economic modelling suggests the world could face a financial loss equivalent to repeating the 2008 global financial crisis annually by 2050 if no action is taken.
TB is now one of the world’s top contributors to AMR-related mortality, and traditional approaches relying solely on new antibiotics cannot keep pace with the rate of bacterial adaptation.
Targeted drug delivery enables extending the lifespan of existing drugs, restoring the potency of those compromised by resistance, and reaching sites that conventional therapeutics cannot.
Instead of relying on ever-stronger antibiotics, which take a decade or more to develop, WADDP designed a tiny 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. Macrophages are immune cells where tuberculosis bacteria hide and multiply.
Inside this particle, bedaquiline is safely packaged and released slowly once it enters the cell, allowing the drug to act exactly where it is needed and for much longer.
In laboratory studies using both porcine and human pericardium, the nanoparticle worked the same way across tissue types. “This is an important sign that it could translate to real clinical use. The particles moved bedaquiline steadily across the membrane without damaging or weakening the tissue,” says Choonara.
This breakthrough for heart-related TB is part of a bigger wave of TB nanomedicine coming out of WADDP. The team has also been developing polydopamine (PDA) nanoparticles. These are a novel type of tiny carriers designed to solve problems that ordinary TB drugs can’t. One of the challenges has been getting medicine into the hard, scar-like structures, known as granulomas, where TB bacteria hide.
These particles can also carry multiple types of payloads simultaneously, including imaging agents and immune-boosting molecules. This means they could one day help doctors both see and treat TB more precisely, while reducing toxicity and improving how well patients can stick to treatment.
“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.
What makes WADDP’s work globally significant is its focus on diseases and anatomical challenges that disproportionately affect low- and middle-income countries. TB pericarditis, for example, 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 the relevant tissues at therapeutic concentrations. Localised, controlled drug delivery systems address this gap directly.