A Groundbreaking Advance from Wits University in the Fight Against TB

The University of the Witwatersrand (Wits) in Johannesburg, South Africa, is at the forefront of innovative research tackling one of the country's most pressing health challenges: tuberculosis (TB). A novel inhalable nanosystem developed at the Wits Advanced Drug Delivery Platform (WADDP) has taken a significant step forward, earning global recognition that positions it closer to market commercialization. This development comes at a critical time, as South Africa grapples with a high TB burden, where the disease claimed over 56,000 lives in 2023 alone.

Dr. Lindokuhle Ngema, a postdoctoral researcher at WADDP, leads this promising project under the supervision of Professor Yahya Choonara, the platform's director. Their work focuses on transforming TB treatment by delivering medication directly to the lungs via inhalation, potentially revolutionizing care for millions affected worldwide, particularly in high-incidence regions like southern Africa.

The Persistent TB Crisis in South Africa and Beyond

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, spreads through airborne droplets from coughs, sneezes, or speech. Despite the Bacillus Calmette-Guérin (BCG) vaccine administered to most South African infants, its protection fades by adolescence, leaving adults vulnerable. In 2024, the World Health Organization (WHO) African Region reported 2.7 million TB cases and 378,000 deaths, accounting for 25% of the global burden despite declining mortality rates. South Africa continues to make strides, with a 61% reduction in TB incidence since 2015 and improved treatment access, but challenges persist amid poverty, inequality, and co-infections like HIV.

Globally, TB caused 1.23 million deaths in 2024, underscoring the urgency for innovation aligned with the WHO's End TB Strategy, aiming for an 80% reduction in new cases and 90% in deaths by 2030. In low-resource settings, the economic and social toll is catastrophic, fueling the need for patient-friendly therapies.

Limitations of Current TB Treatments

Standard TB therapy requires patients to take four oral drugs—rifampicin, isoniazid, ethambutol, and pyrazinamide—daily for six months. This regimen often leads to poor adherence due to side effects including nausea, liver damage, and peripheral neuropathy. Non-compliance fosters multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), complicating treatment and increasing costs.

• Daily pill burden overwhelms patients, especially in remote or impoverished areas.
• Oral drugs lose potency passing through the liver and bloodstream before reaching lung lesions.
• TB bacteria hide in granulomas—protective lung pockets—evading systemic delivery.

These issues highlight the demand for targeted, simplified delivery systems like inhalables, which could bypass barriers and concentrate drugs at the site of infection.

Wits Advanced Drug Delivery Platform: A Hub of Nanomedicine Innovation

Established at Wits University's Faculty of Health Sciences, WADDP specializes in targeted nanomedicines and advanced drug delivery systems. Directed by Professor Choonara, the platform has produced over 300 publications in high-impact journals spanning pharmaceutical sciences, materials engineering, and nanotechnology. Its multidisciplinary approach integrates polymer chemistry, imaging, and pharmacology to address unmet needs in infectious diseases.

WADDP's TB projects exemplify South African higher education's role in global health solutions. Collaborations with international labs, such as RWTH Aachen University Hospital in Germany, enhance capabilities in experimental molecular imaging.

Meet the Pioneers: Dr. Lindokuhle Ngema and Professor Yahya Choonara

Dr. Ngema, supported by a World Academy of Sciences (TWAS) fellowship, spent three months in Professor Twan Lammers' lab at RWTH Aachen optimizing the nanosystem's drug release. His passion drives the project: “TB is clever. 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.”

Professor Choonara emphasizes translation: “If we want to end TB, we must also address the limitations of one-size-fits-all drug delivery.” Their synergy positions Wits as a leader in precision medicine.

How the Inhalable Nanosystem Works: A Step-by-Step Breakdown

This biocompatible nanocarrier, engineered at the molecular level, encapsulates the four first-line TB drugs. Here's the process:

1. Inhalation: Patients inhale the dry powder via a nebulizer or inhaler, traveling from nose/bronchi to alveoli.
2. Targeting: Nanoparticles (100-200 nm) penetrate deep into lungs, evading mucociliary clearance.
3. Localization: They home in on granulomas, responding to local pH, enzymes, and hypoxia for controlled release.
4. Payload Delivery: Drugs unload gradually, achieving high local concentrations while minimizing systemic exposure.
5. Imaging Confirmation: Nuclear Medicine Research Infrastructure (NuMeRI) at Wits tracks real-time movement.

The system's non-toxicity ensures biocompatibility, with early tests confirming feasibility of a single-dose formulation.

Preclinical Evidence and Optimization Efforts

Early lab results demonstrate the nanosystem's ability to combine drugs effectively, with sustained release profiles optimized in Germany. Real-time nuclear imaging validates lung penetration and granuloma targeting. While human trials are pending, these findings support potential for shorter regimens and reduced resistance.

Related WADDP work on heart TB (pericarditis) uses chitosan-mannose nanoparticles to breach the pericardium, delivering bedaquiline to macrophages—offering a blueprint for multi-site TB therapies.

Global Recognition: Cambridge Impulse Programme Selection

On April 1, 2026, Dr. Ngema was selected for the University of Cambridge’s Maxwell Centre Impulse Programme, partnering with South Africa’s National Research Foundation (NRF)—a historic first. This three-month immersion provides workshops, mentorship, and investor access. Alumni have raised over £300 million, launched 65 companies, and created 1,000 jobs.

“This is an incredible opportunity to get the right support on how to take our innovation from the lab into the commercial space,” says Professor Choonara. Read the full Wits announcement.

Path to Market: Challenges and Opportunities

Transitioning from lab to clinic involves regulatory hurdles, scale-up manufacturing, and clinical trials. The Impulse Programme accelerates this via entrepreneurial training and funding networks. In South Africa, partnerships with the NRF and potential industry collaborators could expedite local trials, addressing the TB Recovery Plan 4.0 goals.

Challenges include ensuring stability for inhalation devices, cost-effectiveness for public health systems, and navigating MDR-TB approvals. Yet, with SA's robust clinical trial infrastructure, commercialization could begin within years.

Implications for South African Higher Education and Research Ecosystem

Wits' achievement underscores South African universities' prowess in biomedical engineering, fostering talent like Dr. Ngema through fellowships and international ties. It bolsters Wits' research profile, attracting funding and collaborations essential for Africa's health sovereignty.

For higher education, such breakthroughs highlight nanotechnology's role in curricula, from pharmacy to engineering, preparing students for global challenges. They also position institutions like Wits as innovation hubs, driving economic growth via spin-offs.

Stakeholder Perspectives and Real-World Impact

Patients stand to benefit most: “We hope this could shorten treatment time, improve adherence, and help limit the rise of drug resistance,” Ngema notes. Policymakers see alignment with national plans, while global partners like Cambridge amplify reach.

In SA townships, where TB ravages communities, easier treatments could slash catastrophic costs, easing healthcare burdens.

Future Outlook: Toward TB Eradication

As Ngema concludes, “TB has taken too many lives for too long. If we can make treatment easier, faster, and smarter, then we’re not just improving outcomes, but restoring hope.” With Cambridge backing, this Wits innovation could redefine TB care, exemplifying higher education's transformative power. WHO TB factsheet details the global context.

Stakeholders urge accelerated funding for similar projects, ensuring African-led solutions for African problems.

Photo by Brian Wangenheim on Unsplash