Bile acid-based polydrug nanoparticles for the treatment of acute liver injury

IF 2.8 4区工程技术 Q2 POLYMER SCIENCE

Macromolecular Research Pub Date : 2024-02-13 DOI:10.1007/s13233-023-00241-7

Hanui Jo, Lipjung Jung, Nuri Kim, Gi-Wook Kim, Dongwon Lee

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引用次数: 0

Abstract

Acute liver failure and non-alcoholic fatty liver disease (NAFLD) are a common chronic liver disease worldwide, causing tremendous clinical burden. Despite the increasing prevalence of these life-threatening liver damages, effective medical treatment has not been established. Here, we developed a new treatment strategy based on ursodeoxycholic acid (UDCA) which is one of bile acids and effective for the liver diseases. We designed poly(ursodeoxycholic acid-oxalate) (PUOX) as a polymer prodrug of UDCA. PUOX has hydrogen peroxide (H₂O₂)-scavenging peroxalate ester bonds and could be formulated into nanoparticles. PUOX nanoparticles released UDCA in a H₂O₂-triggered manner and exerted concurrent antioxidant and anti-inflammatory effects with cytoprotective actions. In mouse models of acute liver failure and NAFLD, PUOX nanoparticles exerted highly potent therapeutic effects without noticeable toxicity. PUOX nanoparticles could be a promising approach to improve the efficacy for various H₂O₂-associated liver disease.

Graphical abstract

Poly(ursodeoxycholic acid-oxalate) (PUOX) is a H₂O₂-responsive polymeric prodrug of UDCA. PUOX nanoparticles exert potent cytoprotective effects in liver diseases such as fatty acid and drug-intoxicated acute liver failure.

Abstract Image

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用于治疗急性肝损伤的胆汁酸基多药纳米粒子

急性肝衰竭和非酒精性脂肪肝是全球常见的慢性肝病，造成了巨大的临床负担。尽管这些危及生命的肝损伤的发病率越来越高，但有效的药物治疗方法尚未确立。熊去氧胆酸是胆汁酸的一种，对肝脏疾病有效。我们设计了聚熊去氧胆酸草酸盐（PUOX）作为 UDCA 的聚合物原药。PUOX 具有清除过氧化氢（H2O2）的过硫酸盐酯键，可配制成纳米颗粒。PUOX 纳米颗粒以 H2O2 触发的方式释放 UDCA，并同时发挥抗氧化和抗炎作用以及细胞保护作用。在急性肝衰竭和非酒精性脂肪肝小鼠模型中，PUOX 纳米粒子发挥了强效治疗作用，且无明显毒性。PUOX 纳米颗粒是一种具有 H2O2 反应性的 UDCA 聚合原药。PUOX 纳米颗粒对脂肪酸和药物中毒性急性肝衰竭等肝病具有强效的细胞保护作用。

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

Macromolecular Research 工程技术-高分子科学

CiteScore

4.70

自引率

8.30%

发文量

100

审稿时长

1.3 months

期刊介绍： Original research on all aspects of polymer science, engineering and technology, including nanotechnology Presents original research articles on all aspects of polymer science, engineering and technology Coverage extends to such topics as nanotechnology, biotechnology and information technology The English-language journal of the Polymer Society of Korea Macromolecular Research is a scientific journal published monthly by the Polymer Society of Korea. Macromolecular Research publishes original researches on all aspects of polymer science, engineering, and technology as well as new emerging technologies using polymeric materials including nanotechnology, biotechnology, and information technology in forms of Articles, Communications, Notes, Reviews, and Feature articles.