Ulcerative colitis (UC) is a chronic inflammatory with intestinal mucosal injury disease, and there are no fully effective and safe therapeutic strategies in currently clinical practice. Herein, this work highlights the successful development of an oral colon-targeting hydrogel (WEMT-GEL) using oxymatrine (OMT) and water-extractable arabinoxylan (WEAX) for UC robust targeting therapy. The porous and isomerized spatial network structure formed via enzymatic oxidative cross-linking reactions endows the hydrogel with excellent OMT solubility and responsive release characteristics. Rheological, stability, and mucosal tests confirmed its injectability and colon-targeting adhesion capability, making it suitable for oral administration. Furthermore, WEMT-GEL maintains intestinal barrier integrity via enhanced expression of Claudin-1, Occludin-3, and ZO-1, as well as decreases the release of pro-inflammatory factors by reducing the expression levels of MyD88, thereby exhibiting higher mucosal injury repair and persistent anti-inflammatory capability than free OMT and Mesalazine (5-ASA) in UC. Importantly, WEMT-GEL can improve the pharmacokinetics and biodistribution of OMT and enhance its biosafety by decreasing the content of the toxic metabolite matrine (MT). Therefore, such an oral colon-targeting hydrogel may open a new avenue for robust UC therapy and greatly advance the clinical application of OMT.
[1]Anhui Univ Chinese Med, Sch Pharm, Hefei 230012, Anhui, Peoples R China.
[2]Wannan Med Coll, Yijishan Hosp, Drug Clin Trial Inst, Wuhu 241001, Anhui, Peoples R China.
[3]Chinese Acad Sci, Hefei Canc Hosp, Hefei 230012, Anhui, Peoples R China.
[4]Anhui Prov Key Lab Res & Dev Chinese Med, Hefei 230012, Anhui, Peoples R China.
[5]Anhui Prov Key Lab Pharmaceut Preparat Technol & A, Hefei 230012, Anhui, Peoples R China.
(8.0+极速模式)