Bacteria-triggered drug release system clears preclinical tests

Researchers have developed a hydrogel that releases its payload when exposed to enzymes produced by certain bacteria, opening the door to a smart drug delivery system that could help minimize the risk of drug resistance. 

Some bacterial pathogens become drug resistant by making enzymes that break apart the beta-lactam rings found in many antibiotics. Writing in the journal ACS Applied Materials, researchers explained how they have hijacked that resistance mechanism to develop a hydrogel that releases its antibiotic payload when exposed to beta-lactamase enzymes.

“We’ve developed a bacteria-triggered, smart drug-delivery system,” Anita Shukla, an associate professor at Brown University’s School of Engineering, said in a statement. “Our hypothesis is that technologies like this, which reduce the amount of drug that’s required for effective treatment, can also reduce both side effects and the potential for resistance.”

Shukla, who led the material’s development, worked with colleagues to create hydrogels that degrade specifically in the presence of beta-lactamases. The researchers used a responsive crosslinker to enable the hydrogel to react to the enzymes and validated the approach in in vivo and in vitro studies. 

By encapsulating fluorescent polystyrene nanoparticles in the hydrogel, the researchers showed that the rate of release of the payload tracks the loss of wet mass, indicating that the process is triggered by the enzymes. Hydrogels that lacked the responsive crosslinker remained stable and retained their payloads in the presence of the enzymes and the bacteria that produce them.  

Shukla sees potential to translate the concept to the clinic and is working toward that goal. In humans, the technology could facilitate the development of wound dressings that quickly deliver an antibiotic in response to emergent infections but keep hold of the payload in other circumstances to minimize the risk of unnecessary exposure and drug resistance.