Abstract
Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflamma-tion of the colon and disrupted intestinal function.Ramulus mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products Administration in 2020 for treat-ing type 2 diabetes mellitus.Accumulated evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in UC.However,the treatment of UC faces challenges due to low drug delivery efficiency and short retention time.To overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel contain-ing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407 and 188.The thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5 ℃,a short gelation time of 64 s,a pH range of 7-10,high moisturizing capability exceeding 90％,and moderate mechanical strength of 4-5 s.In a rat model with UC,the in situ thermo-sensitive hydro-gel significantly extended the retention time at the colonic site and enabled sustained release after rectal administration.Symptoms of UC were markedly reduced following rectal administration of SZ-A thermo-sensitive hydrogel.Furthermore,the release of inflammatory factors,such as interleukin-1β(IL-1β),IL-6,IL-18,tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1),significantly de-creased in the SZ-A thermo-sensitive hydrogel group.The integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive hydrogel.In conclusion,rectal administration of SZ-A in situ thermo-sensitive hydrogel effectively alleviated UC symptoms,inhibited the secretion of inflammatory factors,and promoted the repair of the colonic mucosal barrier.This approach holds promise as a potential treatment for UC.
基金项目
National Natural Science Foundation(82304393)
National Natural Science Foundation(China)
Beijing Nova Program(Z211100002121127)
Beijing Nova Program(20220484219)
Beijing Nova Program(China)
Beijing Natural Science Foundation(L212059)
Beijing Natural Science Foundation(China)
CAMS Innovation Fund for Medical Sciences(2021-I2M-1-028)
CAMS Innovation Fund for Medical Sciences(China)
NETL
NSTL
万方数据