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An organic molecule composed of simple sugars could become a powerful weapon in the fight against growing resistance to antibiotics, according to EU-funded researchers who have come up with a new targeted technique of administering drugs to treat deadly tuberculosis and other deadly pathogens.
The EU-funded CYCLON HIT project has studied cyclodextrins – cyclic oligosaccharides whose molecular composition is similar to common table sugar – as a nanotechnology support for antibiotics and other drugs. They discovered that cyclodextrin nanocarbons can be developed not only to effectively encapsulate and protect antibiotics to fight resistant bacteria, but also that these molecules also possess unique antimicrobial properties.
We have taken a totally novel approach in which cyclodextrins are not simply used as nanocarriers of drug combinations, but also play an active role in the fight against infection by interfering with the mechanism by which bacteria invade the cells. "
Ruxandra Gref, Project Coordinator, National Center for Scientific Research in France
By tackling TB, one of the leading causes of death in the world, making more than 1.5 million lives each year, the CYCLON HIT team has studied a method for Introduce antibiotic-containing cyclodextrin nanoparticles directly into the lungs. Mycobacterium tuberculosis the pathogen accumulates in humans. This highly specialized bacterium uses part of the cell membrane called lipid rafts to penetrate the lung tissue where it can settle inside defensive cells called macrophages, effectively hiding in the body's immune system.
By using this ingenious mechanism, the pathogen invades and persists inside the macrophages, despite their role in the death of foreign bodies. We found that artificial cyclodextrins also localized preferentially on lipid rafts and acted as a shield against the penetration of pathogens without any toxicity to the body, "says Gref.
Cyclodextrins can therefore be designed to fulfill two vital functions: to prevent pathogens from invading cells and to administer antibiotics and other drugs to infected cells, thus constituting a powerful double-acting weapon against disease.
More targeted treatment, less side effects
In addition, a patented nanoparticle developed by CYCLON HIT researchers based on β-cyclodextrin nanoparticles could allow the administration of antibiotic combinations directly into the lungs via an inhaler rather than patients ingesting slow-acting pills and less effective.
Following the failure of first-line antibiotics, multidrug-resistant TB is currently being treated with chemotherapy or with second-line antibiotics such as ethionamide in combination with other drugs. However, patients often have difficulty adhering to regimens that may require more than 10,000 tablets over a two-year period, often with debilitating side effects.
"Modified cyclodextrins have been able to incorporate antibiotics, preserving their activity and transmitting them safely to infected cells," says Gref. "Tests on animal models show that this approach achieves higher drug concentrations at the target site and fewer systemic side effects for the patient."
While multidrug-resistant TB was a key test for CYCLON HIT researchers, their synthetic cyclodextrin nanocarriers could also be deployed against a range of other pathogens, such as Salmonella typhimurium, responsible for severe gastroenteritis; Staphylococcus aureusopportunistic pathogen badociated with cutaneous and respiratory infections; and the types of Gram-negative bacteria most involved in nosocomial infections.
Since all species of bacteria continually mutate under the selective pressure of antibiotics, resulting in multidrug resistance and potentially incurable disease, sustained research efforts are needed to develop new methods to help prevent disease. Administer effective treatments.
To this end, the CYCLON HIT project laid the foundation for ongoing research into the broad potential of cyclodextrins through a training program for 11 young experienced researchers and 5 experienced young researchers, supported by the interdisciplinary expertise of 12 institutes research and innovative SMEs in Europe. .
According to Gref, collaborations continue on several fronts beyond the end of the Marie-Curie Initial Training Network project. Members of the project consortium are currently seeking partnerships with companies to further develop and commercialize nanotechnology.
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