An iron-based compound encapsulated in lipid nanoparticles completely eliminated tuberculosis in the lungs of mice after 30 days of treatment, according to a study by the Tuberculosis Research Laboratory at the Araraquara School of Pharmaceutical Sciences of São Paulo State University (FCFAr-UNESP) in Brazil. The study was supported by FAPESP and published in the journal ACS Omega . The results suggest a possible new path for shorter, less toxic, and more effective therapies against resistant bacteria, one of the greatest challenges currently facing the fight against the disease.
Although tuberculosis has been known for centuries and is curable, it is still the deadliest bacterial infection in the world. Standard treatment requires at least six months of daily use of at least four antibiotics, and it can take up to two years when there is resistance to the traditional regimen. This makes adherence difficult, contributing to treatment abandonment and failure.
“The disease is curable, but the treatment is long and intense. Patients take several antibiotics every day, which can cause side effects and affect the kidneys and liver,” explains Fernando Rogério Pavan , study advisor and coordinator of the Tuberculosis Drug Research area at Rede-TB .
The World Health Organization (WHO) estimates that without treatment, tuberculosis can be fatal in up to 50% of cases. Conversely, when the treatment regimen is followed correctly, around 85% of patients are cured. However, the epidemiological scenario in Brazil underscores the need for new drugs to combat the disease. The Ministry of Health recorded 84,308 new cases of tuberculosis in 2024 and 6,025 deaths in 2023, marking the highest numbers in over two decades. These are the most recent data, released in 2025.
Despite free treatment being available through the SUS (the acronym for Brazil’s national public health network, Sistema Único de Saúde ), the researcher explains that proper adherence is especially challenging in vulnerable populations, such as homeless people and those with alcohol dependence. “There are patients who stop taking antibiotics in the middle of the cycle, which leads to bacterial resistance. As a result, many patients end up with no therapeutic options, as the bacteria are resistant to everything available. And that person can transmit this resistant strain to another, creating an even more dangerous cycle,” Pavan points out.
Study idea
For about 20 years, the group led by Pavan has been studying the possible actions of molecules against tuberculosis. This time, in the doctoral research of Fernanda Manaia Demarqui , the idea was to focus on the substance ferroin (scientific name: [Fe(phen)₃]²⁺, or FEP), a very old compound that has been around since the 1950s and is traditionally used in chemical synthesis.
The proposal stemmed from drug repositioning – testing known substances for new therapeutic uses. “We didn’t invent a new molecule. We took an old, inexpensive, water-soluble substance and tested it for tuberculosis. When we saw antimicrobial activity, we thought, ‘This could become a thesis,’” says the researcher.
Laboratory tests showed that FEP strongly inhibits the tuberculosis bacillus and enhances the action of rifampicin and pretomanid, two drugs used to treat the disease. Additionally, the group discovered the mechanism by which the substance acts.
According to Pavan, microscopy and genomic sequencing revealed significant damage to the cell wall of the bacteria, indicating a mechanism of action similar to penicillins. “We discovered that it acts by inhibiting cell wall synthesis. Microscopy shows that the morphology of the bacteria is completely altered, and mutations in its genome correspond to cell wall proteins,” Pavan explains.
Since FEP is an “unstable” substance that could degrade in the stomach, the researchers encapsulated it in lipid nanoparticles (LNP@FEP), which act as a controlled-release “package.” This improved its stability and duration of action in the body. “This capsule protects the substance and allows for gradual release, keeping the compound active for longer. It’s a simple formulation made with cholesterol and phosphatidylcholine that’s inexpensive and easy to produce,” says the researcher.
The next step was to test the compound on animals. The animals were divided into groups of seven mice infected with Mycobacterium tuberculosis . Half of the mice were treated conventionally, and the other half received the compound. After 30 days, complete elimination of the lung infection was observed with both free and encapsulated FEP. This surpassed the performance of isoniazid, one of the standard antibiotics used in the SUS.
“The result surprised us very positively because we were hoping to see some reduction in the bacterial load. But the tests showed that the compound eliminated everything. We found no bacilli in the lungs. In the group treated with the conventional antibiotic, there was a reduction in the bacilli load, as expected,” he reports.
Despite the encouraging results, it is not yet possible to discuss clinical applications. Toxicity and pharmacokinetic studies must be conducted, as well as more robust trials, including models of resistant tuberculosis and cases of chronic infection. However, Pavan points out that the fact that the compound is not patented may facilitate future progress toward industrial development. “This may be of particular interest to the public sector. If it works, it’ll be possible to transform the substance into a drug at low cost.”
If new studies confirm the efficacy and safety of the compound in humans, Pavan expects it to pave the way for shorter, safer treatments with greater patient adherence, which would reduce the risk of resistance and the impact of the disease in the country. “We already know the main thing: it works. Now, we need to adjust the dosage and duration of use, conduct repeat tests, and move forward. But seeing total elimination in animal models gives us hope,” he concludes.
About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe .
ACS Omega
[Fe(phen)3]2+ and [Fe(phen)3]2+-Loaded Nanostructured Lipid System: In Silico, In Vitro, and In Vivo Efficacy against Mycobacterium tuberculosis
27-Nov-2025