As superbugs become increasingly dangerous to human health, NC State researchers have developed a soft material that can store drugs that can treat infections without the risk of antimicrobial resistance.
With his colleague Christopher Gorman of the Department of Chemistry and students Ryan Smith and Juliana O’Brien, Stefano Menegatti, a university faculty scientist and an associate professor of chemical and biomolecular engineering, developed new dendrimers — highly structured macromolecules — that act like glue around nanoparticle templates. Such templates include bacteriophages, which are viruses that can infect and attack harmful bacteria in the body. While they can be an alternative to traditional antibiotics, they can be difficult to formulate and stabilize as a drug. To remain safe and effective, therapeutic bacteriophages must be protected from environmental changes.
Menegatti and his team found that dendrimers in combination with short chains of amino acids or peptides can surround nanoparticles and keep them stable under different conditions. Their team calls these dendrimers DendriPeps. Because nanoparticles are suspended in water, these soluble DendriPeps keep them in a closed, stable system.
“These dendrimer coatings retain the water content in a virus while acting as a proton sponge, protecting the virus from salt or pH changes,” Menegatti said. “It’s a soft but impenetrable barrier. It provides a nice environment for the virus.”
Once DendriPeps has coated nanoparticles, localized shear triggers their release and their therapeutic activity. Soft materials can be designed to respond physically and chemically to stimuli such as temperature, pressure and moisture. Shear is an ideal stimulant for drug delivery applications as it is nearly ubiquitous throughout the body. Eyelids cause shear when blinking; waste slides down the intestinal wall during digestion; shear occurs when something is rubbed against the skin. This allows DendriPeps to treat local infections.
“Shear is often a forgotten stimulus,” Menegatti said. “With this invention, we wanted to fill that gap and Dendrieps presented a great opportunity to do that.”
When a cluster of DendriPep-coated nanoparticles is sheared, it degranules, releasing the individual particles. These particles, in turn, can deliver a therapeutic charge or, like the bacteriophages, infect and kill dangerous bacteria. When therapeutic action is not required, the shear is removed and the particles are recoated with DendriPeps and reluster. This stops the release of the charge.
This formulation can protect bacteriophages. This provides a way to replace antibiotics in some critical applications: The widespread use of antibiotics has developed superbugs — bacteria that are resistant to standard doses of antibiotics. The research team is also developing more DendriPep-based nanomedicines to deliver novel drugs such as viral vectors in gene therapy.
In recent years, Menegatti has been honored as a Goodnight Early Career Innovator and NC State Faculty Scholar. He has also received an ALCOA Foundation Research Achievement Award, a Chancellor’s Innovation Fund grant, and an NSF Early Career Award. Currently, his research has shifted to technology for the production of gene therapy and the creation of more efficient production processes. It is in the same vein as his dendrimer research: he looks for ways to overcome natural and systematic hurdles in biomedicine. His goal is to improve the production of and access to better medicines.
“DendiPeps could be the missing link in materials science to make therapeutic viruses the center of next-generation antimicrobials and drugs,” Menegatti said.
Bacterial Viruses: Faithful Allies Against Antibiotic Resistance
Provided by North Carolina State University
Quote: Researcher Develops Soft Material to Preserve Biological Medicines (2022, Jan 12) Retrieved Jan 12, 2022 from https://phys.org/news/2022-01-soft-material-biological-medicines.html
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