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

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Chinese Chemical Letters 2024年第6期35卷 462-468页

作者： Yu Yan Jiawei Song Dongdong Liu Zihan Liu Jialing Cheng Zhiyang Chen Yanfang Yang Weizhe Jiang Hongliang Wang Jun Ye Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China College of Pharmacy Guangxi Medical UniversityNanning 530021China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and disrupted intestinal *** mori(Sangzhi)alkaloids(SZ-A),derived from twigs of mulberry,were approved by the National Medical Products administration in 2020 for treating type 2 diabetes *** evidence has confirmed that SZ-A also alleviates non-alcoholic fatty liver disease and ameliorates inflammation,indicating its potential to address inflammation in ***,the treatment of UC faces challenges due to low drug delivery efficiency and short retention *** overcome these challenges,an injectable and adherent in-situ thermo-sensitive hydrogel containing SZ-A was developed for rectal drug delivery,utilizing the thermo-sensitive polymers Poloxamer 407and *** thermo-sensitive hydrogel system was designed with a moderate gelation temperature of 32±0.5℃,a short gelation time of 64 s,a p H range of 7-10,high moisturizing capability exceeding 90%,and moderate mechanical strength of 4-5 *** a rat model with UC,the in situ thermo-sensitive hydrogel significantly extended the retention time at the colonic site and enabled sustained release after rectal *** of UC were markedly reduced following rectal administration of SZ-A thermosensitive ***,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 decreased in the SZ-A thermo-sensitive hydrogel *** integrity of the colonic mucosal barrier was significantly enhanced following the application of SZ-A thermo-sensitive *** 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 *** approach holds promise as a potential treatment for UC.

关键词： Ulcerative colitis SZ-A Thermo-sensitive hydrogel rectal administration Alleviation of inflammation Mucosal barrier repair

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Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2732-2747页

作者： Bo Xiao Yuqi Liang Ga Liu Lingshuang Wang Zhan Zhang Libin Qiu Haiting Xu Sean Carr Xiaoxiao Shi Rui LReis Subhas CKundu Zhenghua Zhu Department of Gastroenterology the First Affiliated Hospital of Nanchang UniversityNanchang 330006China College of Sericulture Textileand Biomass SciencesSouthwest UniversityChongqing 400715China Department of Neurology School of MedicineEmory UniversityAtlantaGA 30322USA Atlanta Veterans Affairs Medical Center DecaturGA 30033USA Department of Surgery School of MedicineEmory UniversityAtlantaGA 30322USA Bs Research Group I3Bs—Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkBarcoGuimaraes 4805-017Portugal

The progression of ulcerative colitis(UC)is associated with immunologic derangement,intestinal hemorrhage,and microbiota *** traditional medications mainly focus on mitigating inflammation,it remains challenging to address multiple ***,a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO_(2) nanospheres with Cu_(2)O *** resulting CaO_(2)–Cu_(2)O possessed a desirable diameter(291.3 nm)and a uniform size *** could be efficiently internalized by colonic epithelial cells and macrophages,scavenge intracellular reactive oxygen/nitrogen species,and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 *** nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen *** administration of CaO_(2)–Cu_(2)O could stanch the bleeding,repair the disrupted colonic epithelial layer,and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation,anti-oxidation,wound healing,and ***,it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria(e.g.,Odoribacter and Bifidobacterium)and decreasing the abundances of harmful bacteria(e.g.,Prevotellaceae and Helicobacter).Our gas-driven CaO_(2)–Cu_(2)O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

关键词： Nanomotor Anti-inflammation Blood coagulation Immune regulation Hematopexis Microbiota rebalance Ulcerative colitis rectal administration

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