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用于溃疡性结肠炎治疗的益生菌和大黄素的结肠黏膜下层靶向递送

Colonic Submucosa Targeted Delivery of Probiotic and Rhein for Ulcerative Colitis Treatment.

作者信息

Li Lingqiang, Dai Linxin, Lin Meisi, He Shuang, Du Hongye, Lin Dasheng, Wang Yanbin, Zhang Fenglian, Tao Sian, Sun Xiaoluo, Huang Xinggui, Liu Haihui, Wang Qian, He Lingling, Wu Kunhe, You Jieshu, Zhang Minyue, Fu Chaomei, Tu He, Ye Naijing, Liu Jibin, Gao Fei

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy / School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, China.

Chengdu Huashen Technology Group Co., Ltd., Chengdu, 611137, China.

出版信息

Adv Sci (Weinh). 2025 Aug;12(30):e2409711. doi: 10.1002/advs.202409711. Epub 2025 May 9.

DOI:10.1002/advs.202409711
PMID:40344311
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12376669/
Abstract

Ulcerative colitis (UC) is a chronic disease. A significant challenge for the management of UC is to achieve delivery of drugs to the multi-layer colonic barriers, as existing drugs are difficult to penetrate these depths. In this study, a novel drug delivery system using yeast cell wall microparticles (YPs) are developed to co-encapsulate Bacillus subtilis (BS) and Rhein (Rh) termed Rh-YBS. This system specifically targets colonic microfold cells, enabling direct delivery of BS to the colonic submucosa. Additionally, Rh enhances BS colonization in the submucosa through floral regulation. Studies indicate that Rh-YBS can effectively reach and proliferate within the submucosa in vivo. In a DSS-induced UC mouse model, Rh-YBS stimulates the CGRP-related neural pathway; BS activation in the submucosa leads to increased CGRP secretion, prompting goblet cells to secrete mucus and thereby repairing the mucosa. Furthermore, the Rh-YBS also provide a preventive benefit against UC. In summary, Rh-YBS represents an innovative drug delivery system for mucosal repair in UC treatment, activating a unique mechanism involving the CGRP-related neural pathway.

摘要

溃疡性结肠炎（UC）是一种慢性疾病。UC治疗面临的一个重大挑战是如何将药物递送至多层结肠屏障，因为现有药物难以穿透这些深度。在本研究中，开发了一种使用酵母细胞壁微粒（YPs）的新型药物递送系统，用于共包封枯草芽孢杆菌（BS）和大黄酸（Rh），称为Rh-YBS。该系统特异性靶向结肠微褶细胞，能够将BS直接递送至结肠黏膜下层。此外，Rh通过调节菌群增强BS在黏膜下层的定植。研究表明，Rh-YBS在体内能够有效到达黏膜下层并在其中增殖。在DSS诱导的UC小鼠模型中，Rh-YBS刺激CGRP相关神经通路；黏膜下层的BS激活导致CGRP分泌增加，促使杯状细胞分泌黏液，从而修复黏膜。此外，Rh-YBS对UC也具有预防作用。总之，Rh-YBS是一种用于UC治疗中黏膜修复的创新药物递送系统，激活了一种涉及CGRP相关神经通路的独特机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/f1e65c249788/ADVS-12-2409711-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/e9265d8299fa/ADVS-12-2409711-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/0c1c27e1df93/ADVS-12-2409711-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/8476c684d62e/ADVS-12-2409711-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/3e1905f7a18e/ADVS-12-2409711-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/2919e97bca1b/ADVS-12-2409711-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/5ac5db14fa78/ADVS-12-2409711-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/aef5a67f5c2f/ADVS-12-2409711-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/f1e65c249788/ADVS-12-2409711-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/e9265d8299fa/ADVS-12-2409711-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/0c1c27e1df93/ADVS-12-2409711-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/8476c684d62e/ADVS-12-2409711-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/3e1905f7a18e/ADVS-12-2409711-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/2919e97bca1b/ADVS-12-2409711-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/5ac5db14fa78/ADVS-12-2409711-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/aef5a67f5c2f/ADVS-12-2409711-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b229/12376669/f1e65c249788/ADVS-12-2409711-g003.jpg

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[1]
Colonic Submucosa Targeted Delivery of Probiotic and Rhein for Ulcerative Colitis Treatment.

Adv Sci (Weinh). 2025-8

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本文引用的文献

[1]
Exploring precision treatments in immune-mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery.

Exploration (Beijing). 2024-5-24

[2]
Discovery of vitexin as a novel VDR agonist that mitigates the transition from chronic intestinal inflammation to colorectal cancer.

Mol Cancer. 2024-9-13

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Research (Wash D C). 2024-8-23

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Targeted Screening from Highly Colitis-Resistant Pigs Can Alleviate Ulcerative Colitis in Mice.

Research (Wash D C). 2024-7-16

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

Acta Pharm Sin B. 2024-6

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Gingerenone A Attenuates Ulcerative Colitis via Targeting IL-17RA to Inhibit Inflammation and Restore Intestinal Barrier Function.

Adv Sci (Weinh). 2024-7

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EClinicalMedicine. 2024-3-15

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Chronic abdominal pain in inflammatory bowel disease: a practical guide.

Frontline Gastroenterol. 2023-10-11

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Enzyme-like biomimetic oral-agent enabling modulating gut microbiota and restoring redox homeostasis to treat inflammatory bowel disease.

Bioact Mater. 2024-1-28

[10]
Bacteroides fragilis toxin expression enables lamina propria niche acquisition in the developing mouse gut.

Nat Microbiol. 2024-1

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