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用于清除活性氧和抗炎协同作用以减轻急性肺损伤的可吸入多刺激敏感姜黄素-海藻酸钠纳米凝胶

Inhalable multi-stimulus sensitive curcumin-alginate nanogels for scavenging reactive oxygen species and anti-inflammatory co-ordination to alleviate acute lung injury.

作者信息

Cai Jinyun, Zhong Haiyi, Luo Jianwei, Huang Xinghai, Xu Qiuting, Li Peiyuan

机构信息

College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China.

College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China.

出版信息

Int J Biol Macromol. 2024 Dec;283(Pt 4):137816. doi: 10.1016/j.ijbiomac.2024.137816. Epub 2024 Nov 19.


DOI:10.1016/j.ijbiomac.2024.137816
PMID:39571867
Abstract

Acute lung injury (ALI) is one of the most common and extremely critical clinical conditions, which progresses with an inflammatory response and overproduction of reactive oxygen species (ROS), leading to oxidative damage to the lungs. Curcumin (Cur) has great potential in treating ALI due to its excellent antioxidant and anti-inflammatory effects. In this study, Cur and alginate were cross-linked by zinc ions and intermolecular hydrogen bonding to form an inhalable aqueous nanogel system to overcome Cur's low solubility and bioavailability. Cur-alginate (ZA-Cur) nanogels exhibited superior antioxidant properties and down-regulated inflammation-associated factors in vitro with controlled-release behavior under multi-stimulus conditions such as temperature, pH, and ions. Meanwhile, the nanogels system could effectively scavenge cellular ROS to repair oxidative stress damage. In a mice model of ALI, tracheal nebulised inhalation of ZA-Cur nanogels down-regulated the expression of inflammation-related genes such as TNF-α, IL-1β, and IL-6, as well as modulated MDA content and CAT activity to attenuate oxidative stress injury, showing promising lung-protective effects. In conclusion, this work developed inhalable ZA-Cur nanogels to decelerate the progression of lesions in ALI by scavenging intracellular ROS and alleviating inflammation simultaneously, which may be a promising strategy for treating ALI.

摘要

急性肺损伤(ALI)是最常见且极其危急的临床病症之一,其会随着炎症反应和活性氧(ROS)的过量产生而进展,导致肺部氧化损伤。姜黄素(Cur)因其出色的抗氧化和抗炎作用,在治疗ALI方面具有巨大潜力。在本研究中,Cur与海藻酸盐通过锌离子和分子间氢键交联,形成可吸入水性纳米凝胶系统,以克服Cur的低溶解度和低生物利用度问题。Cur-海藻酸盐(ZA-Cur)纳米凝胶在体外表现出优异的抗氧化性能,并在温度、pH值和离子等多刺激条件下具有控释行为,可下调炎症相关因子。同时,该纳米凝胶系统能够有效清除细胞内ROS,修复氧化应激损伤。在ALI小鼠模型中,经气管雾化吸入ZA-Cur纳米凝胶可下调TNF-α、IL-1β和IL-6等炎症相关基因的表达,并调节丙二醛含量和过氧化氢酶活性,减轻氧化应激损伤,显示出良好的肺保护作用。总之,本研究开发了可吸入的ZA-Cur纳米凝胶,通过同时清除细胞内ROS和减轻炎症来减缓ALI病变进程,这可能是一种治疗ALI的有前景的策略。

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