Micromotors neutralize gastric acid and release drugs depending on pH
San Diego, Calif. January 24, 2017 -- Tiny "submarines" that speed independently through the stomach, use gastric acid for fuel (while rapidly neutralizing it), and release their cargo precisely at the desired pH -- though it may sound like science fiction, this is a new method for treating stomach diseases with acid-sensitive drugs introduced by nanoengineers at the University of California San Diego.
The technique is based on proton-driven micromotors with a pH-dependent polymer coating that can be loaded with drugs. The work was published Jan. 20 in the journal Angewandte Chemie International Edition.
|Artist rendering: microsopic submarines for your stomach|
Though gastric acid is useful for digestion and protection from pathogens, it can be destructive to orally administered, pH-sensitive pharmaceuticals, including protein-based drugs or some antibiotics. A coating resistant to gastric juices is sufficient to protect substances intended to work in the intestines. However, if a drug needs to be activated in the stomach, for instance to treat stomach ulcers or Helicobacter pylori bacteria infection, it is usually combined with proton pump inhibitors to block production of acid. When used over longer periods, these can cause some side effects in patients, including headaches, diarrhea, fatigue, and in some severe cases, anxiety, depression, or rhabdomyolysis (a muscle disease).
With their micromotors, a team led by nanoengineering professors Liangfang Zhang and Joseph Wang at the UC San Diego Jacobs School of Engineering has introduced a novel approach for the neutralization of gastric acid that avoids side-effects and simultaneously acts as a drug transport mechanism that releases its cargo only when the required pH is reached.
The micromotors are 20-micrometer-sized magnesium spheres coated with a nanolayer of gold, followed by a pH sensitive polymer into which a drug payload can be embedded. In this study, researchers embedded the polymer coating with a dye called rhodamine 6G as a model payload. Because the spheres lie on a glass support during the coating process, a small spot on the magnesium core remains uncoated. At this spot, an electrochemical reaction occurs, consuming protons and forming magnesium ions and releasing tiny bubbles of hydrogen gas.
The bubbles propel the motors. This motion results in effective mixing of the liquid. This causes the reaction to proceed rapidly. Less than 20 minutes after administering the motors, the stomach environment reaches a neutral pH value. Once this is reached, the polymer dissolves and releases the payload. In addition, the propulsion increases penetration of the microtransporter into the gastric mucosa, which increases the amount of time that the payload is retained in the stomach. The micromotors are biocompatible and safe to use in the stomach. Stomach function is not affected and the normal pH value is re-established within 24 hours.
Full paper: "Micromotors Spontaneously Neutralize Gastric Acid for pH-Responsive Payload Release." Authors of the study are: Jinxing Li*, Pavimol Angsantikul*, Wenjuan Liu*, Berta Esteban-Fernández de Ávila*, Soracha Thamphiwatana, Mingli Xu, Elodie Sandraz, Xiaolei Wang, Jorge Delezuk, Weiwei Gao, Liangfang Zhang and Joseph Wang.
*These authors contributed equally to this work.
This work is supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense (grant no. HDTRA1-12-1-0002 and HDTRA1-14-1-0064) and by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (award no. R01DK095168).