Gel for ulcers
Biologists have learned how to treat ulcers with hydrogel
Vasilisa Raldugina, N+1
Chinese scientists have developed and tested a bioadhesive hydrogel on pigs that promotes the healing of stomach ulcers due to pH-independent and ultrafast gelation, according to Science Translational Medicine (Xu et al., Bioadhesive hydrogels demonstrating pH-independent and ultrafast gelation promote gastric ulcer healing in pigs).
The gel is able to form even in an acidic environment and is retained on the ulcer site for at least 48 hours. Biologists believe that their development opens up new prospects in the treatment of gastrointestinal diseases, the therapy of which was difficult due to the harsh dynamic conditions of the gastrointestinal mucosa.
Hydrogels are widely used in medicine, including for the delivery of medicines and their placement at the destination. To enhance the interaction between the tissue and the hydrogel, its formation is often induced in situ, delivering the components necessary for the formation of the gel directly to the desired site. However, this is not so easy to do in the stomach – the movement of the walls and constant secretion prevent the formation and retention of gel on the ulcer, interfering with healing. This leads to a significant loss of both the mass of the hydrogel and the therapeutic load, thereby jeopardizing the results of the entire treatment.
Therapeutic effects on the gastrointestinal tract are associated with a high risk of complications - some studies cast doubt on the safety of common drugs. A good alternative solution may be the development of a biomaterial that can be quickly formed and fixed in the harsh dynamic conditions of the stomach, but so far it has not been possible to find such an optimal method for the treatment of gastroenterological diseases.
A group of scientists led by Xiayi Xu from the Chinese University of Hong Kong has created a hydrogel that, thanks to easy endoscopic delivery and strong adhesion to ulcer tissues, offers an alternative to the usual treatment with gastroprotectors.
The authors decided to use catechol-based hydrogels as a basis, which are firmly attached to both organic and inorganic surfaces due to imitation of a typical amino acid in the composition of the mussel leg protein. They are able to form quickly in alkaline conditions, but when exposed to oxidants, their adhesion decreases. But this effect, as it became known a few years ago, can be combated with the help of a reducing thiourea group (NCSN). The researchers synthesized polymer precursors by sewing catecholic and thiourea groups to the backbone of hyaluronic acid. To obtain the desired hydrogel, they sprayed an oxidizer over the solution, as which sodium peridiotate was selected.
To test the effectiveness of the development, scientists artificially created stomach ulcers in pigs and randomly divided them into three groups: a control group, a group without positive control, treated with gastroprotectors (sucralfate) and an experimental group exposed to hydrogel.
The researchers used endoscopic delivery of hydrogels to the affected areas for rapid protection and further acceleration of wound healing. The experimental group of pigs induced gelation of HA-Cat-NCSN in the stomach by delivering precursors and oxidizer through separate catheters. After 48 hours, the experimental group was compared with the control group by immunohistochemical staining for induced nitric oxide synthase, a marker of inflammation, the expression of which was less in those areas of the ulcer that were covered with hydrogel.
In the treatment group, sucralfate wrapped in gauze was injected through an endoscope and fixed at the site of the ulcer with endoscopic clamps. Follow-up was carried out every week for a 14-day period to assess the healing of the ulcer. On day 14, pigs were sacrificed, ulcer tissues were fixed with formalin for 24 hours, and then filled with paraffin for blind histological analysis.
The ulcer index (the product of the longest and shortest ulcer radii) in the experimental group was significantly lower than in the control group both on day 7 (P<0.05) and on day 14 (P<0.05), whereas the difference between the control group and the group without positive control on day 14 was insignificant (P>0.05).
The formed hydrogel quickly adhered to the areas of the stomach ulcer, providing a protective barrier for at least 48 hours, regardless of gastric peristalsis, pH and harsh environment, which led to accelerated healing. The scientists also found that the hydrogel creates a protective barrier that prevents the penetration of external catabolic factors and the accumulation of growth factors around the ulcer area, which suppressed inflammation.
Biologists noticed that the therapeutic effectiveness of sucralfate was achieved due to its precise delivery to the site of the ulcer, whereas a typical oral administration cannot guarantee such an effective localization and, therefore, in reality this method could give the worst therapeutic result. They believe that the treatment with the developed hydrogel is, if not superior, then certainly comparable to traditional drug treatment, and suggest that HA-Cat-NCSN will become a promising alternative for the treatment of refractory ulcers in clinical scenarios, and the possibility of its formation in situ provides greater control over the treatment process.
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