In situ polyphenol-adhesive hydrogel enhanced the noncarcinogenic repairing of KGF on the gut epithelial barrier on TNBS-induced colitis rats

Ulcerative colitis (UC) is a chronic recurrent disease affecting the gastrointestinal tract especially colorectum. Keratinocyte growth factor (KGF) plays the vital roles in maintaining the colonic mucosal barrier. The poor stability and off-target of KGF were two hindering factors for its clinical application. Herein, in situ hydrogel (PE) with mucoadhesive ability was constructed by using temperature-sensitive poloxamer and EGCG as hydrogel-forming material and adhesive enhancer, respectively. Incorporation of EGCG led to the slight decrease of the gelled temperature and shortened the gelled time of PE hydrogel. When the concentration of EGCG is 0.1 %, PE hydrogel exhibits the suitable viscosity of 280 +/- 20 Pa center dot s and the strong adhesive force of 725 +/- 25 mN. KGF was soluble in cold PE solution to obtain KGF-loaded PE hydrogel (KGF@PE). PE hydrogel could improve the stability of KGF in vitro. KGF@PE not only could recover greatly the body weight of TNBS-induced rats but also repair their colonic morphology and goblet cell function. Moreover, the potential of repairing the epithelial barrier was indicated by upregulating tight junction proteins. Importantly, the safety of KGF@PE hydrogel for colitis was also confirmed on AOM/DSS-induced mice models. Conclusively, KGF@PE may be a promising therapeutic platform without obvious side effect for ulcerative colitis.

Automated summary

In this study, an in situ hydrogel (PE) with mucoadhesive ability was successfully constructed using temperature-sensitive poloxamer and EGCG as hydrogel-forming material and adhesive enhancer, respectively. The incorporation of EGCG improved the stability of KGF and shortened the gelled time of PE hydrogel. KGF@PE demonstrated promising therapeutic effects on ulcerative colitis, including recovering body weight, repairing colonic morphology and function, and upregulating tight junction proteins, with no obvious side effects observed in mice models.