A novel nano-drug delivery system of glycyrrhetinic acid-mediated intracellular breakable brucine for enhanced anti-hepatitis B efficacy.

IF 2.3 4区医学 Q3 ENGINEERING, BIOMEDICAL Journal of Biomaterials Applications Pub Date : 2024-08-01 Epub Date: 2024-05-15 DOI:10.1177/08853282241254750

Qingxia Guan, Yumeng Liu, Zhaorui Xia, Yue Zhang, Liping Wang, Yanhong Wang, Shujun Zou, Shaowa Lv, Xiaoying Zhou

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Abstract

Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3'-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC₅₀ values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.

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一种新型的甘草酸介导的细胞内可断裂布鲁氨酸纳米给药系统，可增强抗乙型肝炎的疗效。

背景：甘草次酸介导的布鲁氨酸自组装纳米细胞通过改善布鲁氨酸的水溶性、短半衰期、毒性和副作用，增强了其抗乙型肝炎的特性。布鲁氨酸（Brucine，B）是一种吲哚生物碱，提取自麝香草科植物 Strychnos nux-vomica的种子。目的：为了评估布鲁氨酸-甘草次酸-聚乙二醇-3,3'-二硫代二丙酸-甘油单硬脂酸酯（B-GPSG）治疗乙型肝炎的疗效，研究其对 d-半乳糖胺引起的急性肝损伤的保护潜力及其抗肝癌活性。研究设计：体内和体外实验中使用的 B-GPSG 浓度均为 0.63 毫克/毫升。大鼠注射 d-GalN（450 毫克/千克）作为肝损伤模型。大鼠被分为正常组、模型组、阳性组、阳性对照组、B-PSG 组和 B-GPSG 组。体外实验使用表达 HBV HepG2.2.15 的肝癌细胞。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑（MTT）检测、平板克隆、Hoechst 染色和流式细胞术探讨 B-GPSG 抗乙型肝炎的机制：与模型组相比，B-GPSG组大鼠肝脏系数降低（4.59±0.17 vs 5.88±0.42），大鼠肝匀浆中MDA含量降低（12.54±1.81 vs 23.05±2.98），SOD活性升高，大鼠血清中ALT和AST活性降低。在体外，B-GPSG 组的 IC50 值降低。B-GPSG 组能有效抑制 HepG2.2.15 细胞的增殖和迁移。结论B-GPSG纳米微球的保肝作用归因于其由GA介导的肝脏靶向作用以及与布洛芬的协同作用，这表明其具有治疗乙型肝炎的潜力，这一进展为中药和纳米药物在抗乙型肝炎中的应用提供了新的可能性。

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来源期刊

Journal of Biomaterials Applications 工程技术-材料科学：生物材料

CiteScore

5.10

自引率

3.40%

发文量

144

审稿时长

1.5 months

期刊介绍： The Journal of Biomaterials Applications is a fully peer reviewed international journal that publishes original research and review articles that emphasize the development, manufacture and clinical applications of biomaterials. Peer-reviewed articles by biomedical specialists from around the world cover: New developments in biomaterials, R&D, properties and performance, evaluation and applications Applications in biomedical materials and devices - from sutures and wound dressings to biosensors and cardiovascular devices Current findings in biological compatibility/incompatibility of biomaterials The Journal of Biomaterials Applications publishes original articles that emphasize the development, manufacture and clinical applications of biomaterials. Biomaterials continue to be one of the most rapidly growing areas of research in plastics today and certainly one of the biggest technical challenges, since biomaterial performance is dependent on polymer compatibility with the aggressive biological environment. The Journal cuts across disciplines and focuses on medical research and topics that present the broadest view of practical applications of biomaterials in actual clinical use. The Journal of Biomaterial Applications is devoted to new and emerging biomaterials technologies, particularly focusing on the many applications which are under development at industrial biomedical and polymer research facilities, as well as the ongoing activities in academic, medical and applied clinical uses of devices.