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具有增强生物利用度的丁酸钠负载微球用于肠道屏障损伤的靶向治疗

Sodium Butyrate-Loaded Microspheres With Enhanced Bioavailability for Targeted Treatment of Intestinal Barrier Injury.

作者信息

Lv Yanwei, Jiang Mengni, Ouyang Yongliang, Zheng Xiaoyi, Zhang Liang, Yao Jinpeng, Hu Lianghao, Zhao Jiulong, Li Zhaoshen, Wang Shige

机构信息

Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai, 200433, China.

School of Materials and Chemistry, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai, 200093, China.

出版信息

Adv Healthc Mater. 2025 Apr;14(9):e2402773. doi: 10.1002/adhm.202402773. Epub 2024 Dec 4.

Abstract

Intestinal barrier dysfunction is related to diseases such as inflammatory bowel disease (IBD) and severe acute pancreatitis (SAP). Butyrate and its derivatives (e.g., sodium butyrate (SB)) can alleviate gut inflammatory responses. Nevertheless, these substances usually cannot fully exert protective effects due to low bioavailability. This research aimed to offer microspheres for treating intestinal barrier injury. Sodium alginate solution is prepared to dissolve SB, followed by mixing with chitosan (CS)-protocatechuic aldehyde (PA)/calcium chloride solution. The required CS-PA/calcium alginate/SB (CPC/SB) microspheres are formed in this manner. Subsequently, the therapeutic effects of CPC/SB microspheres on intestinal barrier injury through in vivo dextran sulfate sodium salt (DSS)-induced IBD and sodium taurocholate (STC)-induced SAP models is explored. Results: The CPC/SB microspheres exhibited excellent antioxidant properties. In vivo bioluminescence imaging experiment confirmed the microspheres effectively targeted the inflammatory gut in IBD. Further in vivo experimental results indicated the microspheres significantly repaired intestinal barrier damage, exerting protective effects in IBD and SAP. Additionally, 16S rDNA sequencing explained the microspheres can regulate the balance between harmful and beneficial bacteria (such as Alistipes, Odoribacter, and Rikenellaceae RC9). This study provides a possible synthetic strategy of microsphere carriers to serve as a potential therapeutic tool for intestinal barrier injury.

摘要

肠道屏障功能障碍与炎症性肠病(IBD)和重症急性胰腺炎(SAP)等疾病相关。丁酸盐及其衍生物(如丁酸钠(SB))可减轻肠道炎症反应。然而,由于生物利用度低,这些物质通常无法充分发挥保护作用。本研究旨在提供用于治疗肠道屏障损伤的微球。制备海藻酸钠溶液以溶解SB,然后与壳聚糖(CS)-原儿茶醛(PA)/氯化钙溶液混合。以这种方式形成所需的CS-PA/海藻酸钙/SB(CPC/SB)微球。随后,通过体内葡聚糖硫酸钠(DSS)诱导的IBD和牛磺胆酸钠(STC)诱导的SAP模型,探索CPC/SB微球对肠道屏障损伤的治疗效果。结果:CPC/SB微球表现出优异的抗氧化性能。体内生物发光成像实验证实微球有效地靶向IBD中的炎症肠道。进一步的体内实验结果表明微球显著修复了肠道屏障损伤,在IBD和SAP中发挥保护作用。此外,16S rDNA测序表明微球可以调节有害菌和有益菌(如Alistipes、Odoribacter和Rikenellaceae RC9)之间的平衡。本研究提供了一种微球载体的可能合成策略,以作为肠道屏障损伤的潜在治疗工具。

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