Intestine-Targeted Explosive Hydrogel Microsphere Promotes Uric Acid Excretion for Gout Therapy
© 2023 Wiley-VCH GmbH.
Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 3 vom: 12. Jan., Seite e2310492 |
---|---|
1. Verfasser: | |
Weitere Verfasser: | , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2024
|
Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
Schlagworte: | Journal Article gout hydrogel microspheres immobilized uricase intestinal uric acid excretion Uric Acid 268B43MJ25 Dopamine VTD58H1Z2X Urate Oxidase mehr... |
Zusammenfassung: | © 2023 Wiley-VCH GmbH. Uric acid metabolism disorder triggers metabolic diseases, especially gout. However, increasing uric acid excretion remains a challenge. Here, an accelerative uric acid excretion pathway via an oral intestine-explosive hydrogel microsphere merely containing uricase and dopamine is reported. After oral administration, uricase is exposed and immobilized on intestinal mucosa along with an in situ dopamine polymerization via a cascade reaction triggered by the intestinal specific environment. By this means, trace amount of uricase is required to in situ up-regulate uric acid transporter proteins of intestinal epithelial cells, causing accelerated intestinal uric acid excretion. From in vitro data, the uric acid in fecal samples from gout patients could be significantly reduced by up to 37% by the mimic mucosa-immobilized uricase on the isolated porcine tissues. Both hyperuricemia and acute gouty arthritis in vivo mouse models confirm the uric acid excretion efficacy of intestine-explosive hydrogel microspheres. Fecal uric acid excretion is increased around 30% and blood uric acid is reduced more than 70%. In addition, 16S ribosomal RNA sequencing showed that the microspheres optimized intestinal flora composition as well. In conclusion, a unique pathway via the intestine in situ regulation to realize an efficient uric acid intestinal excretion for gout therapy is developed |
---|---|
Beschreibung: | Date Completed 19.01.2024 Date Revised 19.01.2024 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-4095 |
DOI: | 10.1002/adma.202310492 |