Hope for a new treatment option for the painful intestinal inflammation caused by ulcerative colitis: Researchers have developed a liquid containing medication that can be injected directly into the inflamed areas of the colon using an enema and turns into a stable gel there. When stuck to the site of action, it can then continuously release the active ingredients and calm the inflammation, as experiments on model animals show. This means that a therapeutic approach with fewer side effects is now in sight, say the scientists.
Crampy abdominal pain, diarrhea, weight loss and even severe debilitation: anyone who suffers from ulcerative colitis has to deal with serious symptoms and health risks. The exact causes of this relatively common chronic inflammatory bowel disease are still unclear. Basically, the inflammation that occurs in episodes is attributed to a combination of immune system disorders and other factors. So far, therapy has been largely limited to treating the areas in the colon or rectum affected by the inflammation.
But modern medicine also faces considerable problems. In order to achieve calming effects, very high doses of active ingredients must reach the affected areas. If medications are administered in the form of tablets or injections, they are distributed throughout the body in high concentrations – sometimes with dire consequences. “For many patients suffering from ulcerative colitis, the side effects of an orally taken active ingredient may outweigh the therapeutic benefit,” says senior author Paola Luciani from the University of Bern.
A self-forming “gel patch” instead of tablets etc
An option to use the medication as directly as possible at the site of action would therefore be ideal. However, introducing them into the colon using a suppository or enema has so far proven to be a less than practical solution. The required volume quantities and exposure times are problematic with these dosage forms; the active ingredients are usually excreted too quickly. Luciani and her colleagues’ solution approach is now based on the application of an initially liquid carrier substance for the medication, which then turns into a solid gel on the intestinal wall. The material is a formulation based on special lipids – fat-like molecules that also play an important role as building elements of many biological structures.
For their concept, the researchers used the ability of the monoacylglycerol lipid monolinolein to change from a liquid to a stable gel state in certain formulations when heated. Specifically, the team has now developed a version of this material that is liquid at room temperature and solidifies at body temperature. This allows the substance to be injected into the inflamed area of the colon using an enema. The body temperature then causes it to form into a tough and tight gel. The biodegradable and well-tolerated material can then remain attached to the site of action for at least six hours. During this time, the active ingredients can be continuously and optimally dosed into the inflamed tissue, the scientists explain.
Initially, tests of the method on artificial membranes and intestinal tissue samples delivered promising results. The team then moved on to experiments on mice to study ulcerative colitis: They develop intestinal inflammation that is comparable to that in humans. When testing the system, the researchers used two active ingredients in their gel formulation that are already approved for the treatment of the disease in humans. However, when taken in tablet form, they lead to serious side effects.
Successful test on “colitis mice”
The use of self-forming gel patches in the intestine could now circumvent this problem: “The novel dosage form showed very positive results,” says co-author Philippe Krebs from the University of Bern. The health of the treated mice improved significantly: In contrast to control groups, they showed better inflammation levels and the symptoms in the intestinal wall decreased significantly. The positive effect of the treatment was also reflected in an improvement in the general condition of the animals.
The scientists now hope that human patients will soon be able to benefit from the new form of therapy in this way. After further investigations in animal models, the first clinical tests will follow. Co-senior author Simone Aleandri from the University of Bern says: “We are confident that with our gel we can reduce the side effects compared to current therapies. The goal is a patient-friendly colitis therapy that alleviates the symptoms more effectively due to the targeted and continuous delivery of active ingredients,” says the scientist.
Source: University of Bern, specialist article: Nature Communications, doi: 10.1038/s41467-023-39013-3