Cancer drugs get escort from new polymer UB engineers are developing

BUFFALO, NY — You may not have heard of polyethylene glycol (PEG), but chances are you’ve ingested it.

The non-toxic polymer is commonly used to prevent freezer burn in ice cream, keep toothpaste moist, and most importantly, help cancer drugs hit their target and stay in the body longer.

The overabundance of PEG in foods, cosmetics, and pharmaceuticals can cause people to develop antibodies against it. In some cases, this can lead to allergic reactions and even reduced effectiveness of PEG-coated drugs.

That’s why researchers at the University at Buffalo are studying an alternative polymer to escort cancer drugs through the body, known as a zwitterionic polymer.

“The main benefit of the zwitterionic polymer is the immune response. Unlike PEG, there are currently no antibodies for zwitterionic polymers,” says Chong Cheng, PhD, a professor in UB’s Department of Chemical and Biological Engineering, School of Engineering and Applied Sciences (SEAS).

Cheng is the principal investigator of a $2.4 million grant from the National Institute of Biomedical Imaging and Bioengineering, one of the National Institutes of Health.

Co-investigators are Yun Wu, PhD, associate professor in UB’s Department of Biomedical Engineering, a joint program of SEAS and the Jacobs School of Medicine and Biomedical Sciences, and Eugene Y.-X. Chen, PhD, professor in the Department of Chemistry at Colorado State University.

During the four-year grant cycle beginning April 1, the team will investigate whether zwitterionic polymer-drug conjugates (ZPDCs) can serve as a novel drug delivery system for drugs to treat pancreatic cancer, considered the deadliest type of cancer in the human body.

“Our novel ZPDCs address critical challenges facing current drug delivery systems, such as immunogenicity of PEG and co-delivery of drugs with incompatible properties,” Wu said. more effective to cancer patients and ultimately improve patient outcomes.”

Limitations of PEG Drugs

Many targeted cancer therapies come in the form of small molecule drugs, which have a low molecular weight and can therefore enter cells more easily.

“But because small molecule drugs are so small, they are quickly filtered out by the kidney,” Cheng explains. “So they have a pretty narrow therapeutic window to treat the disease.”

PEG is made up of large, water-soluble molecules, so drugmakers attach it to certain drugs like cancer drugs in a process called PEGylation. This prevents the drug from being broken down before it reaches its target and prolongs its circulation in the blood.

PEG’s ability as a hydrating and stabilizing agent has also made it a popular additive for processed food and cosmetics.

While the U.S. Food and Drug Administration classifies PEG as “generally recognized as safe,” up to 72% of people have detectable levels of anti-PEG antibodies, according to a 2016 study in the journal Analytical Chemistry. . According to the study, only a small fraction have enough antibodies to put them at risk of an allergic reaction, but those who do can suffer from rashes, hives and difficulty breathing.

PEG antibodies may have led a small number of people to have allergic reactions to COVID-19 mRNA vaccines from Moderna and Pfizer-BioNTech, both of which use PEG to stabilize its lipid nanoparticles. The Centers for Disease Control and Prevention recommends that people with PEG allergies should not receive a COVID mRNA vaccine.

In addition to causing allergic reactions, PEG antibodies can prevent pegylated drugs from doing their job.

“The PEG antibody will expel a PEG agent from the biological system, and the effectiveness of this delivery system would be significantly limited,” says Cheng. “This is a major limitation of PEG-based therapies.”

Replacement with ZPDCs

There are currently no ZPDCs on the market. Based on a successful proof-of-concept demonstration, the UB-led team will investigate ZPDCs through physicochemical, cellular, and in vivo studies.

In addition to the absence of an immune response, ZPDCs also have other advantages. Cheng says they have high levels of hydration that allow the drugs to stay in the body even longer than pegylated drugs.

“So our therapeutic window can be even wider,” he says.

And while most ZPDCs currently being studied are not biodegradable, Cheng says his team designed their ZPDCs to be biodegradable.

“This is very relevant for biomedical applications, because otherwise ZPDC accumulation in biological systems would lead to side effects,” he says.

Cheng says PEG is still a good approach for most patients, but its continued wide use makes finding a viable alternative all the more crucial.

“It’s a good opportunity to work in interesting directions, with the potential to benefit many people,” Cheng said. “In this way, we increase the effectiveness of their treatment to improve their health and quality of life.”