Researchers at São Paulo State University (UNESP) in Brazil have developed a low-cost technology using nanoparticles loaded with antibiotics and other antimicrobial compounds that can be used in multiple attacks on infections caused by the bacterium responsible for most cases of tuberculosis in an article published in the journal Carbohydrate Polymers. Results from in vitro tests suggest that this could be the basis for a treatment strategy to combat multidrug-resistant bacteria.
According to the Brazilian Ministry of Health, around 78,000 cases of tuberculosis were reported in 2022, 5% more than the previous year and more than any other country in the Americas. In addition to the increase in incidence, the number of cases with multi-resistant strains is also increasing.
The main causative agent of the disease is the bacillus Mycobacterium tuberculosis, one of the deadliest bacteria known to scientists. Transmission occurs through inhalation of bacteria that migrate into the alveoli, causing inflammation of the airways and ultimately destroying the lung tissue.
The use of nanotechnology is one of the novel treatment strategies considered by scientists around the world to be the most promising against multidrug-resistant strains of M. tuberculosis. The UNESP study, funded by FAPESP (projects 20/16573-3, 22/09728-6 and 23/01664-1), analyzed the antitubercular activity of nanoparticles containing N-acetylcysteine (an over-the-counter dietary supplement). chitosan (a natural compound derived from the exoskeleton of shellfish), an antimicrobial peptide originally isolated from the skin of a Brazilian frog species, and rifampicin (an antibiotic commonly used to treat tuberculosis).
The results showed that the nanoparticles significantly inhibited disease progression and overcome resistance to the drug without causing cell damage.
In vitro tests were carried out using M. tuberculosis-infected fibroblasts, the main active cells in connective tissue, and macrophages, cells of the innate immune system and a key component of the first defense against pathogens.
“Rifampicin is considered outdated for certain strains of the bacillus, but in our study we revitalized and optimized it with antimicrobial peptides that have been shown to help fight the disease,” said Laura Maria Duran Gleriani Primo, first author of the article and an undergraduate student at the School of Pharmaceutical Sciences of UNESP with an introductory scientific scholarship.
“These peptides interact with different receptors in different parts of the bacterium, both in the membrane and in the periplasm. We found that they revitalized rifampicin, which became even more active in macrophages,” said Cesar Augusto Roque-Borda, co-author of the study and doctoral student in the UNESP Program for Graduate Studies in Life Sciences and Pharmaceutical Biotechnology. The periplasm is a region of bacterial cells that lies between the inner cytoplasmic and outer bacterial membranes of the cell envelope.
Conventional treatment for tuberculosis requires the simultaneous use of several antibiotics for a period of six months to about two years, depending on the patient’s response and the resistance of the bacterium. The researchers believe their technique will shorten this time.
“From the study, we know that it is possible to introduce a significant concentration of antibiotics and peptides into macrophages – enough to enhance the effect of the treatment,” said Fernando Rogério Pavan, last author of the article and professor at the School of Pharmaceutical Sciences of the UNESP. “Our expectations for future research include using this type of nanotechnology with other drugs and slow-release medications so that patients do not have to take their medications every day.”
The next step is to confirm the in vitro results through in vivo experiments and explore the use of the nanoparticles to combat other diseases that require long-term treatment.
About the 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 researchers affiliated with higher education and research institutions in the Brazilian state of São Paulo. FAPESP recognizes that the best research is only possible through collaboration with the best researchers at international level. Therefore, it has established partnerships with funding agencies, universities, private companies and research organizations in other countries known for the quality of their research, and encourages scientists funded by its grants to further expand their international collaborations. You can learn more about FAPESP at www.FAPESP.br/en and visit the FAPESP news agency at www.agencia.FAPESP.br/en to stay up to date on the latest scientific breakthroughs that FAPESP is helping to achieve through its many programs, awards and research centers. You can also subscribe to the FAPESP news agency at http://agencia.FAPESP.br/subscribe.
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