Minimizing side effects from anti-obesity medication administration using nanogels
The rapid increase in obesity worldwide is now reaching pandemic proportions.
Obesity is recognized as a chronic disease, which is caused by excessive accumulation of fat in the body.
The drugs that are available for the treatment of obesity are administered either orally or subcutaneously, e.g. naltrexone / bupropion, liraglutide, semaglutide. However, patients often suffer from gastrointestinal disorders, with mild symptoms, initially, which is why the administration of the drugs is carried out in small doses and then increased weekly, up to the maximum prescribed dose.
According to a recent study from the University of Massachusetts, Amherst, a nanogel-based carrier was created, the role of which is to transport the anti-obesity drug directly to the liver, without affecting other organs, thus minimizing side effects.
Specifically, the researchers fed a group of mice a diet high in fat, sugar and cholesterol for ten weeks, doubling their weight, while the other group received a healthy diet. The obese mice were administered the drug, embedded in the nanogel, daily via intraperitoneal injection.
It was observed that even when the mice continued to eat a high-fat diet, after five weeks of treatment, the weight of the experimental animals returned to normal levels, their cholesterol levels decreased and liver inflammation subsided. According to the researchers, what was impressive was that all of this was observed with minimal to no side effects.
For this study, a synthetic thyroid hormone mimic was used, which was incorporated into an anionic nanogel, in order to direct the drug directly to the liver cells, thus increasing its effectiveness and reducing side effects.
When the nanogel carrier enters the liver cells, glutathione in the cells breaks down the nanogel, thus releasing the active substance. The drug then activates thyroid hormone beta receptors, resulting in lipid reduction, increased bile acid synthesis, and fat oxidation. Researchers believe that the activation of fat oxidation and increased metabolic rate likely contribute to weight loss.
Synthetic thyroid hormone mimetics, although not highly bioavailable, are promising treatments for metabolic diseases and have been tested in clinical trials for cholesterol reduction and nonalcoholic steatohepatitis.
The researchers emphasize that although it is premature to conduct clinical trials in humans, the results so far are impressive.
If it is proven that the technique of administering active substances using nanogel is safe, the appropriate conditions will be created for the development of new pharmaceutical preparations for the treatment of liver and other diseases.
