Nanoengineers from the University of California at San Diego for the first time demonstrated the use of micromachines to treat bacterial infections in the stomach. These tiny vehicles, each about half the width of a human hair, swim quickly around the stomach, neutralizing stomach acid, and then release their load of antibiotics at the right pH.Nanoengineers at the University of California San Diego have developed the first micromachines for the treatment of bacterial infections. Image: Nanobioelectronics Lab at UC San Diego
The researchers said that this method of delivery using micromachines is a promising new method of treating diseases of the stomach and gastrointestinal tract with acid-sensitive drugs. The key to their success is collaboration between research teams of nanoengineering professors Joseph Wang and Liangfang Zhang at the UC San Diego Jacobs School of Engineering. Wang and Zhang conducted their first micromachine study in vivo, and this study represents the first example of micromachines in the treatment of bacterial infections
Gastric acid can destroy orally administered drugs such as antibiotics and protein-based pharmaceutical preparations. Drugs used to treat bacterial infections, ulcers, and other diseases in the stomach are usually taken with additional substances, called proton pump inhibitors, to suppress the production of stomach acid
. But with prolonged use or high doses, proton pump inhibitors can cause side effects, including headaches, diarrhea and fatigue. In more serious cases, they can cause anxiety or depression.
Micromachines have a built-in mechanism for neutralizing acid in the stomach and effectively delivering their payloads — without the use of proton pump inhibitors.
“This is a one-step micromachine treatment that combines acid neutralization with therapeutic action,” said Berta Esteban-Fernandez de Avila, a graduate student in the Wang research group at the University of California at San Diego and one of the first authors of this article.The micromachine
consists of a spherical magnesium core coated with a protective layer of titanium dioxide, followed by a layer of antibiotic clarithromycin and the outer layer of a positively charged polymer called chitosan, which allows the engines to stick to the wall of the stomach
This binding is also enhanced by the movement of micromachines, which is fed by the stomach's own acid. Magnesium nuclei react with gastric acid, creating a stream of microbubbles of hydrogen that move the engines inside the stomach. This reaction also temporarily reduces the amount of acid in the stomach, raising the pH level sufficient for the micromachines to release the drug and perform the treatment. The normal pH of the stomach is restored within 24 hours.
Researchers tested micromachines in mice with Helicobacter pylori infections
. Micromachines filled with a clinical dose of clarithromycin antibiotic were administered orally once a day for five consecutive days. Subsequently, the researchers evaluated the number of bacteria in each muscle stomach and found that treatment with micromachines was somewhat more effective than administering the same dose of antibiotic in combination with proton pump inhibitors
Micromachines are made of biodegradable materials. Magnesium kernels and polymer layers are dissolved by gastric juice without the formation of harmful residues.
Researchers say that, although the current results are promising, this work is still at an early stage. The team is planning research to better evaluate the therapeutic characteristics of micromachines in vivo and compare them with other standard methods of treating stomach diseases. Researchers are also planning to test various combinations of drugs with micromachines to treat many diseases of the stomach
and in different parts of the gastrointestinal tract. In general, the researchers say that this work opens the door to using synthetic engines as active drug delivery platforms for treating diseases in vivo.