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载有广藿香油纳米乳液的 ROS/Thermo 双重敏感水凝胶用于溃疡性结肠炎。

ROS/Thermo dual-sensitive hydrogel loaded with a nanoemulsion of patchouli essential oil for ulcerative colitis.

机构信息

School of Pharmacy, School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu 611137, China.

School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

出版信息

Int J Biol Macromol. 2024 Nov;281(Pt 4):136542. doi: 10.1016/j.ijbiomac.2024.136542. Epub 2024 Oct 12.

Abstract

Patchouli essential oil (PEO) is acknowledged as a potent contender for the management of ulcerative colitis (UC). However, the limited ability of PEO to be absorbed by the body and its low stability substantially limit its potential uses. Furthermore, UC lesions are mainly concentrated in the rectal and colonic mucosa, with excessive production of reactive oxygen species (ROS). Herein, a nanoemulsion of PEO (PEONE) was developed to enhance the stability and bioavailability of a drug. Subsequently, we developed a novel platform for the rectal administration of a ROS/thermo dual-sensitive Bletilla striata polysaccharide-based hydrogel (RTH) co-loaded with PEONE to efficiently treat UC. As expected, the sol-gel transition of PEONE@RTH, after its intrarectal administration, resulted in its extended presence in the colon and facilitated its attachment to the inflammation site. Moreover, PEONE@RTH alleviated dextran sulfate sodium-induced UC symptoms by suppressing inflammation and oxidative stress, repairing the damage to the intestinal epithelial barrier (claudin-1 and occludin), increasing short-chain fatty acid content and inhibiting the MAPK signalling pathway. Additionally, PEONE@RTH exhibits exceptional safety and biocompatibility. Thus, PEONE@RTH has the potential to provide a novel approach for treating UC and other intestinal disorders characterised by similar clinical conditions.

摘要

广藿香精油(PEO)被认为是治疗溃疡性结肠炎(UC)的有力竞争者。然而,PEO 被身体吸收的能力有限,且其稳定性低,这极大地限制了其潜在用途。此外,UC 病变主要集中在直肠和结肠黏膜,活性氧(ROS)过度产生。在此,开发了 PEO 的纳米乳液(PEONE)以提高药物的稳定性和生物利用度。随后,我们开发了一种直肠给药的新型平台,用于同时负载 ROS/热双敏感白芨多糖水凝胶(RTH)和 PEONE,以有效治疗 UC。正如预期的那样,PEONE@RTH 在直肠给药后发生溶胶-凝胶转变,使其在结肠中的存在时间延长,并有利于其附着在炎症部位。此外,PEONE@RTH 通过抑制炎症和氧化应激、修复肠上皮屏障(闭合蛋白-1 和紧密连接蛋白)损伤、增加短链脂肪酸含量和抑制 MAPK 信号通路来缓解葡聚糖硫酸钠诱导的 UC 症状。此外,PEONE@RTH 具有出色的安全性和生物相容性。因此,PEONE@RTH 有可能为治疗 UC 及其他具有类似临床特征的肠道疾病提供一种新方法。

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