Oral olsalazine/ellagic acid/ZnCl2‐modified in situ-forming hydrogels alleviates anxiety/depression-like symptoms and brain neural activity in colitis mice

Inflammatory bowel disease (IBD) is a kind of chronic non-specific intestinal inflammatory disease, which accompanied by various abnormal psychological states, such as anxiety and depression. Nevertheless, the pathogenesis of IBD with depression is still unclear. Herein, we synthesized an enable a d...

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Main Authors: Tingting Li, Nianlu Li, Haoyu Sheng, Luyao Zhang, Qian Luo, Sashuang Liu, Yijing Zhao, Wenqiang Chen, Dexiang Liu, Zhen Wang
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425006283
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author Tingting Li
Nianlu Li
Haoyu Sheng
Luyao Zhang
Qian Luo
Sashuang Liu
Yijing Zhao
Wenqiang Chen
Dexiang Liu
Zhen Wang
author_facet Tingting Li
Nianlu Li
Haoyu Sheng
Luyao Zhang
Qian Luo
Sashuang Liu
Yijing Zhao
Wenqiang Chen
Dexiang Liu
Zhen Wang
author_sort Tingting Li
collection DOAJ
description Inflammatory bowel disease (IBD) is a kind of chronic non-specific intestinal inflammatory disease, which accompanied by various abnormal psychological states, such as anxiety and depression. Nevertheless, the pathogenesis of IBD with depression is still unclear. Herein, we synthesized an enable a drinkable, liquid in situ-forming hydrogel, which form directly in the stomach through sequential ingestion of a crosslinker solution of CaCl2 and ε-poly-l-lysine (ε-PL), followed by a drug-containing polymer solution of sodium alginate (SA). Using olsalazine (Olsa) and antioxidant (ellagic acid (EA) and ZnCl2) as small molecule drug (referred as Olsa/EA/Zn), the resulting hydrogel (referred as Olsa/EA/Zn@SA/ε-PL hydrogel) could form rapidly in gastric fluid and exhibit remarkable stability under acidic conditions, unique low swelling properties and a rational release of drug in entering the intestine. We demonstrated that the oral administration of drug-loaded in situ-forming hydrogel with excellent antioxidant, anti-inflammatory activities, cytocompatibility, intestinal retention capacity of the drug, significantly enhanced the IBD therapeutic outcomes, and relieve accompanying depression-like symptoms in colitis mice. Overall, this designed in situ-forming hydrogel oral delivery system will open up new pathway in combined gastrointestinal therapy and psychological comorbidities for IBD patients, especially those with dysphagia.
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spelling doaj-art-bb331781fd834901ac450dfa3b794f372025-08-20T02:36:49ZengElsevierMaterials Today Bio2590-00642025-08-013310205810.1016/j.mtbio.2025.102058Oral olsalazine/ellagic acid/ZnCl2‐modified in situ-forming hydrogels alleviates anxiety/depression-like symptoms and brain neural activity in colitis miceTingting Li0Nianlu Li1Haoyu Sheng2Luyao Zhang3Qian Luo4Sashuang Liu5Yijing Zhao6Wenqiang Chen7Dexiang Liu8Zhen Wang9Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR ChinaShandong Provincial Qianfoshan Hospital, Jinan, Shandong, 250012, PR ChinaDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR ChinaDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR ChinaQilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR ChinaDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China; Corresponding author.Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China; Corresponding author. Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, 250012, PR China.Inflammatory bowel disease (IBD) is a kind of chronic non-specific intestinal inflammatory disease, which accompanied by various abnormal psychological states, such as anxiety and depression. Nevertheless, the pathogenesis of IBD with depression is still unclear. Herein, we synthesized an enable a drinkable, liquid in situ-forming hydrogel, which form directly in the stomach through sequential ingestion of a crosslinker solution of CaCl2 and ε-poly-l-lysine (ε-PL), followed by a drug-containing polymer solution of sodium alginate (SA). Using olsalazine (Olsa) and antioxidant (ellagic acid (EA) and ZnCl2) as small molecule drug (referred as Olsa/EA/Zn), the resulting hydrogel (referred as Olsa/EA/Zn@SA/ε-PL hydrogel) could form rapidly in gastric fluid and exhibit remarkable stability under acidic conditions, unique low swelling properties and a rational release of drug in entering the intestine. We demonstrated that the oral administration of drug-loaded in situ-forming hydrogel with excellent antioxidant, anti-inflammatory activities, cytocompatibility, intestinal retention capacity of the drug, significantly enhanced the IBD therapeutic outcomes, and relieve accompanying depression-like symptoms in colitis mice. Overall, this designed in situ-forming hydrogel oral delivery system will open up new pathway in combined gastrointestinal therapy and psychological comorbidities for IBD patients, especially those with dysphagia.http://www.sciencedirect.com/science/article/pii/S2590006425006283Inflammatory bowel diseaseHydrogelInflammationReactive oxygen species
spellingShingle Tingting Li
Nianlu Li
Haoyu Sheng
Luyao Zhang
Qian Luo
Sashuang Liu
Yijing Zhao
Wenqiang Chen
Dexiang Liu
Zhen Wang
Oral olsalazine/ellagic acid/ZnCl2‐modified in situ-forming hydrogels alleviates anxiety/depression-like symptoms and brain neural activity in colitis mice
Materials Today Bio
Inflammatory bowel disease
Hydrogel
Inflammation
Reactive oxygen species
title Oral olsalazine/ellagic acid/ZnCl2‐modified in situ-forming hydrogels alleviates anxiety/depression-like symptoms and brain neural activity in colitis mice
title_full Oral olsalazine/ellagic acid/ZnCl2‐modified in situ-forming hydrogels alleviates anxiety/depression-like symptoms and brain neural activity in colitis mice
title_fullStr Oral olsalazine/ellagic acid/ZnCl2‐modified in situ-forming hydrogels alleviates anxiety/depression-like symptoms and brain neural activity in colitis mice
title_full_unstemmed Oral olsalazine/ellagic acid/ZnCl2‐modified in situ-forming hydrogels alleviates anxiety/depression-like symptoms and brain neural activity in colitis mice
title_short Oral olsalazine/ellagic acid/ZnCl2‐modified in situ-forming hydrogels alleviates anxiety/depression-like symptoms and brain neural activity in colitis mice
title_sort oral olsalazine ellagic acid zncl2 modified in situ forming hydrogels alleviates anxiety depression like symptoms and brain neural activity in colitis mice
topic Inflammatory bowel disease
Hydrogel
Inflammation
Reactive oxygen species
url http://www.sciencedirect.com/science/article/pii/S2590006425006283
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