Hydrogel reduces impact of alcohol in mice

In Raffaele Mezzenga’s lab at the Federal Institute of Technology, Zurich, mice consume a lot of alcohol. Their drunkenness serves a higher purpose: each creature helps test out a new hydrogel designed by Mezzenga and his team to break down alcohol in the gut. In their recent paper, the scientists describe the gel’s remarkable efficiency (Nat. Nanotechnol. 2024, DOI: 10.1038/s41565-024-01657-7).

Researchers in Mezzenga’s lab have long used whey, a watery byproduct of cheesemaking, as a platform for alcohol-busting catalytic reactions. When postdoctoral researcher Jaiqui Su joined the lab, she came up with the idea to create a whey-based gel peppered with iron atoms to act as catalytic sites. Each site is structurally similar to the active site of horseradish peroxidase, and mimic the natural enzyme’s ability to split peroxide into hydroxyl radicals.

The gel can also oxidize alcohol into acetic acid in the presence of peroxide. “It’s a cascading catalytic reaction,” explains Mezzenga, with the more desirable reaction—alcohol oxidation—requiring hydroxyl radicals for initiation. Gold nanoparticles incorporated into the gel reacts with glucose to provide a local source of peroxide high enough to initiate the alcohol reaction but low enough to remain nontoxic.

After designing the gel and characterizing its catalytic abilities, the team decided it was time to test the material’s function in a living system—mice. The researchers fed the hydrogel to one group of mice through a feeding tube then filled the stomachs of all but the control group with 10 g of alcohol for every 1 kg of body weight to mimic acute alcohol toxicity, says Su. Those mice treated with the gel awoke from their drunken slumber two hours before untreated mice. Subsequent blood tests revealed that less alcohol made it into the bloodstreams of the hydrogel-dosed mice.

A second group of mice were fed a diet spiked with ethanol for 16 days to mimic chronic alcoholism, Su says. The mice that received doses of the new hydrogel had significantly less liver and colon damage compared to their untreated peers.

“We certainly did not aim to treat chronic alcohol abuse in mice,” says Mezzenga, “We want to go to humans.”

Minimizing accidental alcohol poisoning like that associated with college parties is the most obvious use for this kind of drug, writes Mack Mitchell, Vice President for Medical Affairs at UT Southwestern Medical Center. But he’s not yet convinced that it would be useful for treating chronic alcohol abuse. The gel won’t break down all the alcohol someone ingests “so people might just drink more” to stay intoxicated, he writes.

Although it’s healthier not to drink alcohol, the hydrogel researchers say that if the mouse model holds in clinical trials, the new hydrogel could be used to minimize the negative physiological effects of long-term alcohol use. Mezzenga is optimistic that they’ll be able to move onto clinical trials soon and, hopefully, “open the floor to a solution to a global problem.”