The lack of effective antibiotics is an increasingly serious threat to global health. Only a few new antimicrobial agents have been able to reach the market in the last decades. The development of new functionalities for antibiotics that are already known – or those that are no longer used due to their toxicity – is one of the strategies to fill this shortage of drugs.
Now an international team including scientists from the University of Barcelona (UB), the Bioengineering Institute of Catalonia (IBEC) and the Jozef Stefan Institute from Slovenia has managed to improve known antibiotics so that they are more effective in many ways smaller doses. This finding opens up the possibility of developing new antimicrobial treatments in an innovative and affordable way.
A simple and inexpensive way to redesign old antibiotics is to incorporate them into complexes that can modify some of their properties (solubility, stability, bioavailability, permeability, etc.) essential for their effectiveness against bacteria. For this reason, Eduard Torrents (of the UB and IBEC) and his colleagues have developed a new ternary complex in which the antibiotic ciprofloxacin binds to the hydrophilic surface of cyclodextrin, which acts as a link between the two molecules, via an amino acid – arginine. Compared to other less stable classical inclusion complexes—which only change the solubility of the antibiotic—the ternary complex synthesized in this study is also more stable and efficient.
This new complex intensifies the drug’s interaction with bacterial membranes and increases its bioavailability in cells, improving its antimicrobial efficacy and safety profile. «Its release is more controlled and enables a more effective effect with a smaller amount. Therefore, the treatment is less toxic to the body,” Torrents explains.
Steps in breaking down the membrane into a vesicle-like structure in a ciprofloxacin-treated Pseudomonas aeruginosa bacterium. (Photos: UB)
“Our redesign system could reduce toxicity or increase penetrating capacity of many antibiotics that have been used for decades and are now obsolete. That way we could take what we already have and repurpose it, improve it to achieve the effective antimicrobial treatments we desperately need,” concludes Torrents.
The study is titled “Development of a cyclodextrin-arginine-ciprofloxacin ternary antibiotic complex with improved stability.” It was published in the journal Communications Biology. (Source: UB)