Nanoparticles with antibacterial action could shorten the duration of tuberculosis treatment

An inexpensive technology involving nanoparticles loaded with antibiotics and other antimicrobial compounds that can be used in multiple attacks against infections by the bacteria responsible for most cases of tuberculosis has been developed by researchers at the University of State of São Paulo (UNESP) in Brazil.

The work is reported in an article published in the journal Carbohydrate polymers. The results of the in vitro tests suggest that this could provide the basis for a therapeutic strategy aimed at combating bacterial multidrug resistance.

According to the Brazilian Ministry of Health, some 78,000 cases of tuberculosis were reported in 2022, 5% more than the previous year and more than in any other country in the Americas. In addition to the increase in incidence, the number of cases involving multidrug-resistant strains is also increasing.

The main agent of the disease is the bacillus Mycobacterium tuberculosis, one of the deadliest bacteria known to scientists. Transmission occurs through inhalation of bacilli, which migrate to the pulmonary alveoli, causing inflammation of the airways and eventually destroying lung tissue.

The use of nanotechnology is one of the new therapeutic strategies considered the most promising by scientists around the world against multidrug-resistant strains of M. tuberculosis. The UNESP study analyzed the anti-tuberculosis activity of nanoparticles including N-acetylcysteine ​​(an over-the-counter supplement), chitosan (a natural compound derived from the outer skeleton of crustaceans), an antimicrobial peptide isolated from origin of the skin of a species of Brazilian frog. and rifampicin (an antibiotic commonly used to treat tuberculosis).

The results showed that the nanoparticles significantly inhibited disease progression and overcame drug resistance without causing cellular damage.

In vitro assays were performed with M. tuberculosis-infected fibroblasts, the major active cells in connective tissue, and macrophages, cells of the innate immune system and a key component of first-line defense against pathogens.

“Rifampicin is considered obsolete for some strains of the bacillus, but in our study we revitalized and optimized it with antimicrobial peptides that have been proven to help fight the disease,” said Laura Maria Duran Gleriani Primo, first author of the article and co-author of the article. undergraduate student at the UNESP School of Pharmaceutical Sciences.

“These peptides interact with various receptors in different parts of the bacteria, both in the membrane and in the periplasm. We found that they revitalized rifampicin, which became even more active inside the macrophages,” said Cesar Augusto Roque-Borda, co-first author of the study. and a Ph.D. candidate in the UNESP Biosciences and Pharmaceutical Biotechnology Graduate Program. The periplasm is a region of bacterial cells located between the inner and outer cytoplasmic bacterial membranes of the cell envelope.

Future prospects

Conventional treatment of tuberculosis involves the concomitant use of several antibiotics for six months to approximately two years depending on the patient’s response and the resistance of the bacteria. The researchers expect their technique to shorten this time frame.

“From the study, we know that it is possible to insert a considerable concentration of antibiotics and peptides into the macrophages, enough to enhance the effect of the treatment,” said Fernando Rogério Pavan, last author of the article and professor at the UNESP School of Pharmaceutical Sciences. . “Our expectations for future research include using this type of nanotechnology with other drugs and slow-release medications so that patients do not need to take their medications every day.”

The next step will be to confirm the in vitro results using in vivo assays and to study the use of nanoparticles to combat other diseases requiring long-term treatment.