Biotechnology

Small particles will deliver TB drugs to the lungs in the future

[ad_1]

The treatment of the dangerous infectious disease tuberculosis faces the challenge of pathogens that often become resistant to some of the common antibiotics.

Researchers at the Karlsruhe Institute of Technology (KIT) in Germany have developed nanoparticles to deliver a new antibiotic directly to the lungs in the future. Surfactants ensure that the highly fat-soluble antibiotics spread very finely in water and can be inhaled. The first tests at the Borstel Research Center, Leibniz Pulmonary Center, revealed the high effectiveness and good compatibility of the antibiotic nanocarriers. This research is published in ACS Nano.

Tuberculosis is an infectious disease with the highest mortality rate in the world. As reported by WHO, tuberculosis infection that is resistant to therapy is increasing. Diseases caused by bacterial infections can also occur in Germany. Tuberculosis is a particular challenge for two reasons. First, the bacteria envelop in tissues, mostly in the lungs, where they may lie dormant for years and cause symptoms long after the primary infection. Second, tuberculosis bacteria are often resistant to two or more common antibiotics. The increasing incidence of therapy-resistant strains is due to insufficient drug concentrations at the site of infection and premature discontinuation of treatment because of the often severe side effects of antibiotics.

Nanomedical approach

Nanomedical approaches can help reduce the further development of resistance. The nanoparticles will be used to deliver new antibiotics directly to the source of infection and infected cells. In this way, the drug concentration can be increased locally in the lungs.

“However, newly developed antibiotics are often lipophilic and fat soluble and cannot or can hardly be administered in water. They are virtually non-absorbable when contained in the stomach, blood or cell fluids,” said Claus Feldmann, head of the research group at KIT’s Institute of Inorganic Chemistry (AOC).

Currently, patients suffering from tuberculosis are treated with high doses for a long time to reach the pathogen. Severe side effects, such as liver damage, often lead to discontinuation of therapy, resulting in further development of resistance. In the future, say the researchers, the nanoparticles will be used for specific delivery of antibiotics.

“We have tested several nanocarriers to transport antibiotics to tuberculosis pathogens in mice. The new nanocarrier developed by our colleagues at KIT convinced me that it is possible to directly deliver high doses of antibiotics to tuberculosis foci in the lung without affecting other organs,” said Ulrich E. Schaible, head of the Cellular Microbiology Group and director of the Borstel Research Center. , Leibniz Lung Center.

The particles developed by KIT can carry high drug concentrations

Researchers at the KIT Institute of Inorganic Chemistry have succeeded in producing nanoparticles that can carry very high concentrations of antibiotics.

“The concentration of antibiotics reaches 99% of the total particle weight,” said Feldmann.

“According to the literature, usually a maximum of only 10% is reached so far.”

KIT’s nanocarrier can be dispersed in water. When inhaled, the aerosol enters deep into the lungs. At the Borstel Research Center, researchers under the direction of tuberculosis expert Schaible, in collaboration with other partners from Germany, Austria and Belgium, tested the effectiveness of nanoparticles with good results in the laboratory and in living organisms.

“Still, more work is needed before these aerosol formulations can be applied to humans,” said Schaible.

Overcoming biological barriers

Amorphous nanoparticles for inhalation contain 69% Bedaquilin concentration or 99% BTZ-043 concentration. Both of these antibiotics are effective against multi-resistant tuberculosis bacteria. Surfactants make antibiotics highly lipophilic dispersing in water. The dispersions with Bedaquilin 4.0 mg/ml or 4.2 mg BTZ-043/ml remained stable for several weeks. When tested on mice, the effectiveness of the nanoparticle dispersion exceeded that of conventional BTZ-043 solutions for pulmonary inhalation by 50%.

Nanocarriers are proven to be able to overcome various biological barriers. High concentrations were measured in the lungs, but not in the liver and spleen.

The work was carried out within the ANTI-TB project funded by the Federal Ministry of Education and Research (BMBF).

KIT and Borstel Research Center have filed a joint patent.

Want to expand your network?

Build relationships with world-leading academic teams across 250+ institutes.

IN SECTION Logo 960x960px Web 72ppi Transparent Thin Border

[ad_2]

Source link

Related Articles

Back to top button