Scientists have discovered that metformin, an ancient drug for diabetes, can help fight antibiotic-resistant bacteria as part of a non-antibiotic antibacterial technology.
A research team in China has reused metformin, a small molecule drug that has been used to treat type II diabetes for more than 50 years, as an additional support for antibacterial treatments. They found that metformin can improve the efficiency and effectiveness of antibacterial treatments for rapid wound healing in mice.
His findings were published in the journal Nano Research this month.
“Antibiotic abuse has caused severe bacterial resistance, with about 1.27 million deaths in 2019 due to multi-drug resistant bacterial infections,” says co-author Linlin Li, a professor at Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences.
“Bacterial resistance poses a deadly threat to human health. Non-antibacterial antibacterial technologies and antibacterial nanoagents with specific catalytic activities not only produce toxic substrates to directly kill bacteria, including antibiotic-resistant bacteria, but can also reduce the risk of bacteria developing drug resistance, “he added.
He explains that chemodynamic therapy “has attracted significant attention since it was developed in 2016 as a potential companion for therapies for cancer, bacterial inactivation and treatments for infectious diseases,” a press release said.
In their study, the authors write that “[r]recently, the development of chemodynamic therapy (CDT) offers a potential approach to fighting bacteria and treating infectious diseases, in which these nanoagents CDT can catalyze the generation of hydroxyl (• OH) radicals to kill bacteria. “
The researchers wanted to test the nanosheets with metformin, so they used mice to simulate a staph infection on their skin. (Nano Research)
Chemodynamic therapy uses nanomaterials that contain transition metals that react with hydrogen peroxide to produce a hydroxyl radical. The hydroxyl radical acts on infected or diseased cells, weakening and killing them, making it possible to treat them directly.
“The reaction generates a toxic hydroxyl radical, which destroys the structure of the cell surface and causes the cell to filter its internal components,” says Li.
“Nanoagents only catalyze the generation of hydroxyl radicals at the site of the tumor or inflamed tissues, so therapy is very specific to reduce off-target toxicity. Bacterial infections are also often accompanied by favorable microenvironmental alterations for in chemodynamic therapy “.
The scientists worked on a twofold solution: one, they had to improve the antibacterial power of a nanoagent, and the second, they had to reduce the toxicity to healthy cells. This risk could be difficult to control, due to the invasive nature of the infection.
“Positively charged parts of molecules, such as quaternary ammonium salts and chitosan, have intrinsic antibacterial effects by adsorption to the bacterial cell wall, producing a compartment resistance effect and ultimately inducing death. bacterial, “says Li.
“Metformin is a positively charged small molecule drug with anticancer, immunomodulatory and antibacterial effects. We speculated that the integration of metformin with a chemodynamic therapy nanoagent would enhance the antibacterial effect.”
The researchers combined metformin with copper chloride and created nanofoules whose surface was covered by metformin molecules, which Li said improved the nanoagent’s positive charge and enhanced the antibacterial effects.
When they performed in vitro tests, they found that the biocompatible nanoplatform has better dispersion, a measure of the heterogeneity of molecule or particle sizes in a mixture, than a nanoagent without metformin and higher antibacterial activity.
“Compared to previous reports of using metformin as an antibacterial agent alone, excellent antimicrobial effects were achieved in our experiments using lower concentrations of nanowires with a very short time to action,” says Li.
According to the press release, he also “noted that they are also studying the effects of metformin in other biomedical applications to develop more therapies.”
The researchers wanted to test the nanosheets with metformin, so they used mice to simulate a staph infection on their skin. Subjects were divided into five groups, receiving a variation of one treatment.
The group of mice that received both metformin nanosheets and additional hydrogen peroxide to improve hydroxyl radical production ended up with the fastest wound healing rate: their wound had closed completely on the 12th of treatment.
Researchers write “In vivo [tested on mice] the results proved it [Cu2(OH)3Cl nanosheets] accelerated tissue regeneration of staphylococcus aureus-infected dermal wounds. “
“This work not only develops a nanoagent for chemodynamic therapy that is effective as an alternative antibacterial agent for treating skin wound infections, but also provides ideas for discovering new uses for old drugs,” says Li.
Source: TRWorld and agencies