Researchers have reduced blood alcohol levels in intoxicated mice by injecting them with nanocapsules containing enzymes that are instrumental in alcohol metabolism. The treatment demonstrates a novel drug delivery technology that could have broad medical applications.
Enzymes are proteins that catalyze a wide range of biological processes in the body, making them attractive candidates as therapeutics. Many important biological functions require precisely arranged groups of different enzymes working in concert, often inside a cellular subcomponent called an organelle. Though researchers have tried for years to develop such complexes in the lab, it has proved extremely difficult to maintain stable proteins and precisely control their size and arrangement.
The new research, which was described today in Nature Nanotechnology, involves packaging multiple enzymes inside a nanoscale shell. The resulting functional enzyme complex, made of a nontoxic polymer, “almost mimics an organelle,” says Yunfeng Lu, a professor of chemical and biomolecular engineering at UCLA, who lead the research with Cheng Ji, a professor of biochemical and molecular biology at the University of Southern California. The capsule stabilizes the proteins and protects them against degrading in the body.
To demonstrate the efficacy of the delivery method, the researchers injected the mice with capsules containing two enzymes. One of them, oxidase, produces hydrogen peroxide, so it has to work in concert with another enzyme that decomposes this potentially harmful by-product. The researchers report that the mice receiving the enzyme treatment saw their blood alcohol content fall quickly and significantly compared with controls.
The advance could open the door to a new class of enzyme drugs, says Lu. Down the road, for example, he envisions an alcohol prophylactic or antidote that could be taken orally. Since alcohol metabolism naturally occurs in the liver, it would “almost be like having millions of liver cell units inside your stomach or in your intestine, helping you to digest alcohol,” he says.
The group is also developing other drugs based on the encapsulation method. For example, it is working with the pharmaceutical company Kythera on a hair-loss prevention drug that would rely on nanocapsules to deliver—through the skin—an enzyme that breaks down dihydrotestosterone (commonly called DHT), which causes male pattern baldness.