Targeted drug delivery increases the potency of antibiotics

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According to the researchers, a new targeted delivery system could offer a way to make antibiotics more effective against pathogens.

Hung-Jen Wu, an associate professor in the department of chemical engineering at Texas A&M University, is working to defeat bacteria that have become resistant to several types of antibiotics.

“These bacteria are not only drug resistant, they are multiresistant,” he says. “This means that several different classes of antibiotics cannot kill them. It has become a very big threat to public health because doctors are unable to effectively treat these diseases with the same drugs used. in the past.

In the past, the medical research community has attempted to overcome antibiotic resistant bacteria by developing new antibiotics. This approach is costly and can take decades to accomplish. Wu takes a different approach. Using a targeted system, it delivers the antibiotics directly to the bacteria, allowing them to have a greater impact on the pathogen.

“By using a targeted delivery system, we can actually reduce the dose of the antibiotic while effectively killing the pathogen,” says Wu.

The idea of ​​using a targeted approach emerged when researchers observed the behavior of Pathogens they were looking to kill. When bacteria enter the body, they use a combination of strong and weak ligand connections to attach to a cell membrane and infect the cell.

Ligands, which are molecular connections that exist on both the bacterium and the cell membrane, allow the two cells to stick together using unique molecular structures. Wu and his collaborators exploit this characteristic of bacteria by using this binding method to efficiently deliver antibiotics directly to bacteria.

“We noticed how the bacteria simultaneously bind to strong and weak ligands in the host cell, and we wondered how we could use it,” says Wu. transportation of drugs.”

Although the medical community had tried using these connections before, the effectiveness was low because researchers focused only on strong ligand pairs.

“What makes our lab unique is our focus on weak ligand pairs,” says Wu. are rare. The abundance of weak ligand pairs makes them more efficient in delivering drugs to the cell.

To facilitate targeted delivery, Wu engineered molecular ligand structures on the outside of antibiotic particles that bind to weak ligand pairs on the bacterial cell membrane. When an antibiotic particle encounters a bacterial cell, the abundance of weak ligand pairs causes the antibiotic particle to adhere to the cell in multiple places, creating a more stable connection.

This allows for more efficient absorption of the antibiotic by the bacterial cell. This rapid absorption of the antibiotic leads to more efficient destruction of the pathogen.

Wu’s research focuses on two types of bacteria, the bacterium that causes tuberculosis, Mycobacterium tuberculosisand one of the major bacterial pathogens that has shown resistance to antibiotics, Pseudomonas aeruginosa. In the future, he hopes to apply his method to other types of bacteria to help slow the spread of other infectious diseases.

“This mechanism was designed to work with all types of bacteria,” says Wu. “When we apply it to other types of bacteria, I can quickly identify ligand pairs. We will be able to effectively treat many types of bacteria with this new tool. »

The search appears in Advanced therapy and Applied materials and ACS interfaces.

The National Institutes of Health, the National Science Foundation and the Men of Distinction Foundation supported the work.

Source: Victor Salazar for Texas A&M University

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