Construction of colon-specific Pickering emulsions with rhein-chitosan conjugated nanoparticles as emulsifier and its application in murine ulcerative colitis.

IF 7.7 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

International Journal of Biological Macromolecules Pub Date : 2025-06-18 DOI:10.1016/j.ijbiomac.2025.145349

Jingjing Niu, Meng Wang, Yinxiong Wang, Bowen Yang, Bo Zhang, Min An, Anqi Lin, Lingxiao Li, Lihong Liu, Zhigang Yang, Yanbin Shi

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引用次数: 0

Abstract

Rhein demonstrates therapeutic advantages in ulcerative colitis treatment through multi-target synergy and multi-pathways, yet its clinical application is limited by poor oral bioavailability due to low solubility and poor medication compliance caused by gastrointestinal irritation. The study constructed a composite oral colon-specific delivery system based on rhein-loaded Pickering emulsions (Rhein@Rh-CS/TPP PEs), in which rhein-chitosan conjugated nanoparticles (Rh-CS/TPP NPs) serving as emulsifier, aiming to enhance rhein' bioavailability, improve its anti-ulcerative colitis efficacy, and reduce side effects. Briefly, rhein was covalently modified onto chitosan to increase hydrophobicity of chitosan, then the synthesized Rh-CS/TPP NPs were served as solid particle emulsifier. The resulting Rhein@Rh-CS/TPP PEs were verified as an oral delivery system with pH-responsive, enzyme-triggered, and bioadhesive properties for colon-specific and sustained release. Rhein exerted synergistic anti-ulcerative colitis effects by inhibiting TLR4/NF-κB/MLCK pathway activation and up-regulating tight junction proteins ZO-1, claudin-3 and occludin. Additionally, the Pickering emulsions significantly improved rhein' bioavailability while mitigating intestinal irritation-induced nutrient loss. The work provides a new strategy for the safe and effective application of insoluble intestinal stimulant drugs in the treatment of ulcerative colitis.

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以大黄聚糖-壳聚糖共轭纳米颗粒为乳化剂的结肠特异性皮克林乳剂的构建及其在小鼠溃疡性结肠炎中的应用。

Rhein通过多靶点协同、多途径治疗溃疡性结肠炎，显示出治疗优势，但由于溶解度低，口服生物利用度差，以及胃肠道刺激引起的用药依从性差，限制了其临床应用。本研究以大黄酸负载皮克林乳剂（Rhein@Rh-CS/TPP PEs）为基础，以大黄酸-壳聚糖共轭纳米颗粒（Rh-CS/TPP NPs）为乳化剂，构建了一种复合口服结肠特异性给药体系，旨在提高大黄酸的生物利用度，提高其抗溃疡性结肠炎的疗效，减少副作用。简单地说，将大黄酸共价修饰在壳聚糖上，提高壳聚糖的疏水性，然后将合成的Rh-CS/TPP NPs作为固体颗粒乳化剂。所得到的Rhein@Rh-CS/TPP PEs被证实是一种口服给药系统，具有ph响应性、酶触发性和生物粘附性，具有结肠特异性和缓释性。Rhein通过抑制TLR4/NF-κB/MLCK通路激活，上调紧密连接蛋白ZO-1、claudin-3和occludin发挥协同抗溃疡性结肠炎作用。此外，皮克林乳剂显著提高了大黄的生物利用度，同时减轻了肠道刺激引起的营养损失。本研究为安全有效地应用不溶性肠道兴奋剂治疗溃疡性结肠炎提供了新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Biological Macromolecules 生物-生化与分子生物学

CiteScore

13.70

自引率

9.80%

发文量

2728

审稿时长

64 days

期刊介绍： The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.