The lack of effective antibiotics is an increasingly serious threat to global health. In recent decades, only a few new antimicrobial agents have been able to reach the market. Designing new functionalities for already known antibiotics —or those that are in disuse due to their toxicity— is one of the strategies to fill this shortage of drugs.
Now, in research carried out by an international team that includes scientists from the University of Barcelona (UB), the Bioengineering Institute of Catalonia (IBEC) and the Jozef Stefan Institute of Slovenia, it has been possible to improve known antibiotics so that they are more effective in much smaller doses. This finding opens the possibility of developing new antimicrobial treatments in an innovative and affordable way.
A simple and inexpensive way to redesign old antibiotics is to include them in complexes capable of modifying some of their properties (solubility, stability, bioavailability, permeability, etc.) that are essential for them to be effective against bacteria. For this reason, Eduard Torrents (from the UB and IBEC) and his colleagues have designed a new ternary complex where the antibiotic ciprofloxacin binds to the hydrophilic surface of cyclodextrin through an amino acid —arginine— that acts as a link between the two molecules. Compared with other less stable classical inclusion complexes —which only modify 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 inside cells, thus improving its antimicrobial efficacy and safety profile. «Its release occurs in a more controlled way and allows it to be more effective with less quantity. Therefore, the treatment is less toxic to the body» explains Torrents.
Steps in the breakdown of the membrane into a vesicle-like structure in a ciprofloxacin-treated Pseudomonas aeruginosa bacterium. (Photos: UB)
“Our redesign system could reduce the toxicity or increase the penetrative capacity of many antibiotic drugs that have been used for decades and are now obsolete. In this way, we could take advantage of what we already have and give it a new use, improve it, to achieve the effective antimicrobial treatments that we urgently need”, concludes Torrents.
The study is titled “Development of a ternary cyclodextrin-arginine-ciprofloxacin antimicrobial complex with enhanced stability.” It has been published in the academic journal Communications Biology. (Source: UB)