In what they are calling a world first, nanoengineers at the University of California San Diego (UCSD) have delivered tiny drug-bearing motors into the stomachs of mice where the devices moved around via bubble propulsion. The locomotion method not only allowed the mini molecular machines to navigate, but it also changed the pH of the stomach to allow the successful dispatch of bug-clobbering antibiotics.
The stomach can be a violent place, especially on delicate drugs prone to disintegrating in its high-acid environment. That's why certain antibiotics need to be given with other drugs known as proton-pump inhibitors that dial back the stomach's production of gastric acid. While this dual-drug approach to fighting infections can be successful, proton-pump inhibitors carry with them negative side effects like fatigue, headaches and gut upset.
To eliminate the need to use the acid-neutralizing drugs, the UCSD researchers created molecular machines — each about half the width of a human hair — that could protect antiobiotics until the devices could temporarily change the stomach's chemistry into a more hospitable environment in which the drugs could work.
Each machine consists of a round magnesium core protected by a layer of titanium dioxide. This is then surrounded by a layer of chitosan, a substance derived from the shells of crustaceans, containing a positive charge that lets the motors stick to the stomach lining. In the study, the motors were also packed with a dose of clarithromycin, an antibiotic used to fight respiratory and skin infections as well as the Helicobacter pylori bacteria, which causes stomach ulcers.
When the motors reached the rodents' stomachs, the magnesium cores reacted with the stomach acid to release a steady stream of hydrogen microbubbles. These bubbles not only propelled the motors but they reduced the acidity of the stomach, increasing the pH to a level that was safe for the antibiotics. At that point, the machines released their bug-fighting payloads.
"It's a one-step treatment with these micromotors, combining acid neutralization with therapeutic action," said Berta Esteban-Fernández de Ávila, a postdoctoral scholar in UCSD research group that carried out the study, and a co-first author of the paper.
The drugs were delivered to the mice in this way for five days in a row. Subsequent analysis of the bacterial count in each mouse stomach showed that the micromotors were slightly more effective in fighting the infection than a combination of proton pump inhibitors and clarithromycin given in tandem. But the micromotor treatment was able to sidestep the potentially negative effects of the inhibitors.
The researchers say that the stomach's pH level returns to normal within 24 hours of a dose.
While the mouse trials were successful, the research team points out that there is still more work to be done before human trials can take place. Next, they are looking to find out how different drug combinations packed into the micromotors could help fight gut-based diseases. They also plan to carry out more studies, to compare the new method against established treatments for stomach diseases.
The work has been published in the journal Nature Communications.
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