DendriPep: Innovative macromolecules that stabilize bacteriophages as a medicine

In the world of booming antimicrobial resistance, scientists worldwide struggle to find a proper method of treating superbugs. Recently, the savior has been recognized globally, and the interest has been reinstated to build on the foundation of what is already known. A virus that is the most abundant entity on this planet turned into an alternative to antibiotics. These viruses have so far saved patients who were in intensive care units where no antibiotic was able to cure them. Despite the trial on ways of commercializing them just like regular antibiotics, phages still suffer many problems provided that they are live particles. One of the significant problems is maintaining phage preparation stability during delivery. Mainly the stability will be influenced by the matrix/media used to suspend phages.

Researchers from New York City State University (NCSU) developed a soft material capable of preserving bacteriophages for therapy. With his colleague Christopher Gorman in the Department of Chemistry and students Ryan Smith and Juliana O’Brien, Stefano Menegatti, a University Faculty Scholar and an associate professor of chemical and biomolecular engineering, developed new dendrimers — highly structured macromolecules — that act as glue around nanoparticle templates. Such templates include bacteriophages, viruses that can infect and attack harmful bacteria in the body. While they can be an alternative to traditional antibiotics, they can be challenging to formulate and stabilize as a medicine. To remain safe and effective, therapeutic bacteriophages need to be protected from environmental changes.

Menegatti and his team found that dendrimers combined with short chains of amino acids, or peptides, can surround nanoparticles and keep them stable in various conditions. Their team calls these dendrimers DendriPeps. As nanoparticles are suspended in water, these soluble DendriPeps keep them in a closed, stable system.

“These dendrimer coatings maintain the water content inside a virus while acting as a proton sponge, shielding the virus from salt or pH changes,” Menegatti said. “It’s a soft yet impermeable barrier. It maintains a nice environment for the virus.”

Once DendriPeps have coated nanoparticles, localized shear triggers their release and therapeutic activity. Soft materials can be designed to respond physically and chemically to stimuli like temperature, pressure, and moisture. Shear is an ideal stimulus for drug delivery applications because it is almost ubiquitous throughout the body. Eyelids cause shear when blinking; waste shears the gut wall during digestion; shear is created when one rubs something onto the skin. This allows DendriPeps to treat local infections.

Microscopic imaging shows how shear degranulates particles that have been coated in Dendripeps.

“Shear is often a forgotten stimulus,” Menegatti said. “With this invention, we wanted to fill that gap, and Dendripeps offered an amazing opportunity to do so.”

When a cluster of DendriPep-coated nanoparticles is sheared, it degranulates, releasing the single particles. These particles can, in turn, release a therapeutic payload or, like the bacteriophages, infect and kill dangerous bacteria. When therapeutic action is not needed, shear is removed, and the particles are recoated with DendriPeps and recluster. This stops the payload release.

This formulation can protect bacteriophages. This offers a way of replacing antibiotics in some critical applications: The widespread use of antibiotics has developed superbugs — bacteria resistant to standard doses of antibiotics. The research team is also developing more DendriPep-based nanomedicines to deliver new drugs like viral vectors in gene therapy.

“DendiPeps could be the missing link in material sciences to make therapeutic viruses the center of the next-generation antimicrobials and drugs,” Menegatti said.

These viruses do not affect human cells and in fact, they have proved to be a promising future in the fight against antimicrobial resistance.

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https://news.ncsu.edu/2022/01/nc-state-researcher-develops-soft-material-to-preserve-biological-medicines/