Unesp Tuberculosis Nanoparticle Research: Iron Compound Eradicates TB in Mice, Opens Path to New Treatments

The Persistent Global and Brazilian Tuberculosis Challenge

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, remains one of the world's deadliest infectious diseases, surpassing even HIV in mortality rates among treatable conditions. According to the World Health Organization, TB claims over 1.3 million lives annually, with treatment regimens lasting six months or more using multiple antibiotics daily. These prolonged therapies often lead to severe side effects on the liver and kidneys, poor patient adherence, and the emergence of drug-resistant strains. 76 97

In Brazil, the situation is particularly acute. The Ministry of Health's 2025 Epidemiological Bulletin reports 85,936 new cases in 2024 alone, alongside 6,025 deaths in 2023—the highest in over two decades. Vulnerable populations, including those experiencing homelessness or alcohol dependency, face heightened risks due to interrupted treatments, perpetuating cycles of resistance and transmission. Brazil's Unified Health System (SUS) provides free treatment, yet detection rates hover around 89%, underscoring the need for innovative, shorter, and less toxic therapies. 98

Unesp's Pioneering Role in Combating TB Through Higher Education Research

The Universidade Estadual Paulista (Unesp), a leading public university in São Paulo state, has been at the forefront of TB research for nearly two decades. At its Araraquara campus, the Faculdade de Ciências Farmacêuticas (FCFAr-Unesp) houses the Laboratório de Pesquisas em Tuberculose, where interdisciplinary teams blend microbiology, pharmacology, and nanotechnology to address this public health crisis. Unesp's efforts exemplify how Brazilian higher education institutions drive impactful science amid resource constraints, fostering collaborations with global partners like the University of Illinois and King's College London. 117

This research not only advances knowledge but also trains the next generation of scientists through graduate programs rated highly by CAPES, Brazil's higher education evaluation agency. For aspiring researchers, opportunities abound in research jobs at institutions like Unesp, where tackling real-world problems like TB can lead to fulfilling careers in academia and pharma.

The Breakthrough: Iron Phenanthroline Complex in Lipid Nanoparticles

The innovation centers on ferroin, chemically denoted as [Fe(phen)₃]²⁺ (FEP), a water-soluble iron-phenanthroline complex discovered in the 1950s for chemical analysis but repurposed here via drug repositioning—a cost-effective strategy in resource-limited settings. FEP targets the TB bacterium's cell wall synthesis, causing morphological damage visible under microscopy and genomic mutations in wall-related proteins. It synergizes with standard drugs like rifampicin and pretomanid, amplifying their efficacy. 76

To overcome FEP's instability in the stomach, researchers encapsulated it in nanostructured lipid systems (NLS@FEP) using simple, inexpensive components: cholesterol and phosphatidylcholine. This formulation ensures controlled release, prolonged activity, and ease of production, ideal for scaling in public health systems.

Step-by-Step Methodology: From In Silico to In Vivo

The study employed a multi-stage approach:

• In silico screening: Computational modeling predicted FEP's binding to TB targets.
• In vitro tests: Assessed antimicrobial activity against M. tuberculosis, confirming cell wall disruption via microscopy and genomic sequencing.
• Formulation development: Encapsulation in lipid nanoparticles for stability.
• In vivo evaluation: Seven mice per group infected pulmonarily; treated daily for 30 days with FEP (free or encapsulated), compared to standard isoniazid or untreated controls. Lungs analyzed post-treatment for bacterial load.

This rigorous pipeline highlights Unesp's integration of computational biology, nanotechnology, and animal modeling—core strengths in Brazilian higher education pharma programs.

Groundbreaking Results: Complete Eradication in Mice Lungs

After 30 days, both free and encapsulated FEP achieved zero detectable bacilli in mouse lungs, surpassing the partial reduction from conventional isoniazid therapy. Researchers were astonished, expecting only modest bacterial load decreases. The lipid encapsulation proved equally effective, validating the delivery system's potential for oral or inhalable use. 76

These outcomes suggest FEP could shorten treatments from 6-24 months to weeks, boosting adherence and curbing resistance—a game-changer for Brazil's SUS.

Spotlight on Visionary Researchers Leading the Charge

Professor Fernando Rogério Pavan, Associate Professor and Full Professor in Microbiology at FCFAr-Unesp, leads the charge. With an h-index of 40 and international collaborations, Pavan coordinates Rede-TB's anti-TB drug research and projects like FINEP/SUS Inova TB for inhalable therapies. PhD student Fernanda Manaia Demarqui executed key experiments. Their work builds on 20 years of Unesp TB studies, demonstrating mentorship's role in higher ed. 117

"We didn't invent a new molecule; we repurposed an old, cheap one," Pavan noted, emphasizing accessibility.Pavan's FAPESP profile

Transformative Implications for TB Treatment and Public Health

Key benefits include:

• Shorter regimens to improve adherence.
• Reduced toxicity versus multi-drug cocktails.
• Low-cost production without patents, suiting public sectors.
• Potential against drug-resistant TB via novel mechanisms.

In Brazil, where TB disproportionately affects marginalized groups, this could save lives and resources. Globally, it aligns with WHO goals for shorter therapies. 76

Explore career advice for roles in such impactful research.

Navigating Hurdles: Toxicity, Resistance, and Path to Clinics

While promising, challenges remain: toxicity profiling, pharmacokinetics, and trials in resistant/chronic TB models. Future phases include dose optimization and preclinical scaling. Unesp's track record positions it well for partnerships.Published in ACS Omega

Unesp Araraquara: Powerhouse of Brazilian Higher Ed Innovation

FCFAr-Unesp's CAPES 7-rated graduate program exemplifies excellence, with projects like inhalable TB meds (Inova TB, R$14M funding). This fosters faculty positions and attracts talent to Brazil's research ecosystem.

FAPESP Funding: Fueling Brazil's Research Engine

FAPESP's support underscores public investment in higher ed. Pavan's grants highlight how state funding amplifies national impact, creating jobs in Brazilian academia.

Future Horizons and Opportunities in TB Research Careers

With clinical trials on horizon, this Unesp breakthrough inspires. Professionals can advance via postdoc jobs or postdoc advice. Check Rate My Professor for Unesp insights, higher ed jobs, and university jobs.