首页|Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis

Simple and versatile in situ thermo-sensitive hydrogel for rectal administration of SZ-A to alleviate inflammation and repair mucosal barrier in ulcerative colitis

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
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.

Ulcerative colitisSZ-AThermo-sensitive hydrogelRectal administrationAlleviation of inflammationMucosal barrier repair

Yu Yan、Jiawei Song、Dongdong Liu、Zihan Liu、Jialing Cheng、Zhiyang Chen、Yanfang Yang、Weizhe Jiang、Hongliang Wang、Jun Ye、Yuling Liu

展开 >

State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100050,China

College of Pharmacy,Guangxi Medical University,Nanning 530021,China

Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation,Institute of Materia Medica,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050,China

National Natural Science FoundationNational Natural Science FoundationBeijing Nova ProgramBeijing Nova ProgramBeijing Nova ProgramBeijing Natural Science FoundationBeijing Natural Science FoundationCAMS Innovation Fund for Medical SciencesCAMS Innovation Fund for Medical Sciences

82304393ChinaZ21110000212112720220484219ChinaL212059China2021-I2M-1-028China

2024

10.1016/j.cclet.2024.109736

中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCD
影响因子：0.771
ISSN：1001-8417
年,卷(期)：2024.35(6)
  • 1