Alternative to proton pump inhibitors
Microdrivers protected medicines from the effects of gastric juice
Oleg Lischuk, N+1
American scientists have developed micro-motors that neutralize acid in the stomach and release drugs at a given acidity value. The results of the work are published in the journal Angewandte Chemie (Li et al., Micromotors Spontaneously Neutralize Gastric Acid for pH-Responsive Payload Release).
The acidic environment in the stomach is necessary for the denaturation of food proteins and the normal operation of the enzyme pepsin that breaks them down. It also kills many food-borne microorganisms. In addition, acid in the stomach neutralizes many medications. Such drugs protect against its action by placing them in an intestinal-soluble shell. However, for acid-sensitive drugs acting directly in the stomach (for example, antibiotics that are used to treat peptic ulcer disease), this method of protection is not suitable. Therefore, they are prescribed in combination with proton pump inhibitors (potassium-proton ATP-aza), which block the synthesis of acid by gastric lining cells. However, these drugs, especially with prolonged use, have serious side effects, which limits their use.
In search of an alternative method of delivering drugs to the gastric wall, employees of the University of California at San Diego have developed micro-motors that use acid as fuel and neutralize it during operation. The basis of such a micromotor is a magnesium sphere with a diameter of about 20 micrometers. These spheres are placed on a glass substrate and covered with a 10-nanometer layer of gold so that the area of the sphere in contact with the glass remains uncoated. A layer of pH-sensitive polymer is applied to the gold layer, which contains the drug and releases it at a given acidity value (pH greater than 5.5).
When ingested in the stomach, uncoated gold magnesium reacts with acid protons, resulting in the formation of hydrogen gas bubbles. Due to the reactive power of these bubbles, micro-motors actively move around the stomach at an average speed of 60 micrometers per second, neutralizing the next protons. Within less than 20 minutes, they raise the pH to a predetermined level (proton pump inhibitors need about an hour for this), after which the polymer breaks down, releasing the drug.
In an experiment on mice, five milligrams of microdrivers in 20 minutes increased the average pH value in the stomach of animals from 1.88 to 7.81, after which a fluorescent dye was released. Due to the movement of microspheres, the delivery of the drug to various areas of the gastric mucosa was more efficient and uniform than with passive diffusion. The acid neutralizing effect was dose–dependent (2.5 milligrams increased the pH to 4.24; 10 milligrams - to 9.43).
Operation of micro-motors with fluorescent paint in the stomach of mice
(drawing from an article in Angewandte Chemie)
The experiment also showed the complete biocompatibility of micro-motors: no side effects of their use were registered during histological examination. The acidity of gastric juice returned to normal values during the day.
Based on the results obtained, the developers called their micro–motors an attractive alternative to proton pump inhibitors (you can add - in everything except cost).
The interest in this development can be increased by data recently obtained by an American research team. Scientists have found that proton pump inhibitors disrupt the work of lysosomes – cellular organelles that purify the cell of obsolete and defective structural elements. Because of this, premature aging of the endothelium (inner lining) of the vessels occurs, which, in turn, increases the risk of dementia, myocardial infarction and renal failure.
Portal "Eternal youth" http://vechnayamolodost.ru
24.01.2017