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新型 HCV 治疗方法的研究:通过环保方法合成的半乳糖化壳聚糖纳米粒子负载 Boscia angustifalia 和 Boscia senegalensis 提取物,用于 HCV 治疗。

Investigation of novel HCV therapies: Boscia angustifalia & Boscia senegalensis extracts loaded on galactosylated chitosan nanoparticles synthesized by eco-friendly method for HCV treatment.

机构信息

Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El Buhouth St, Dokki, 12622 Giza, Egypt.

Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute, Giza, Egypt.

出版信息

Int J Biol Macromol. 2023 Aug 1;245:125420. doi: 10.1016/j.ijbiomac.2023.125420. Epub 2023 Jun 21.

Abstract

Hepatitis C virus (HCV) is a major causative agent of chronic liver diseases including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Treatment of HCV has evolved from early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C after receiving therapy with direct-acting antivirals (DAA) with a 0.5 % chance of the hepatitis C virus recurrence, similar to other chronic viral infections. So, retreatment options following treatment failure have become crucial issues. Hence, this study aims to investigate a new promising therapy for HCV. In the field of nanomedicine, chitosan nanoparticles are well-known delivery systems that are frequently used as polymeric carriers. Galactosylated chitosan nanoparticles have been widely applied in HCV treatment. In this study, we have modified galactosylation by an eco-friendly method using l-ascorbic instead of hazardous reagents and we have loaded it with newly tested two Boscia extracts each in three different concentrations. The synthesized chitosan nanoparticles showed two dispersion peaks, at 196 ± 29 nm and 1.33 ± 0.36 μm, with a zeta potential of +3.3 ± 0.4mV with high stability in a range of 40.7 mV. The percentage of encapsulation of Boscia angustifalia extract was found to be 46.58 ± 1.33 % and for Boscia senegalensis extract was 9.77 ± 0.33 %. The release of Boscia angustifalia extract from the nanoparticles was about 40 % in acidic media after 180 min and about 60 % in normal pH. However, the release of Boscia senegalensis extract was 20 % in acidic media and 56 % in normal media after 24 h. Testing of these two newly developed composites against HCV was carried out using an in vitro system for the production of hepatitis C virus (HCV) which was established by infection of human hepatoma cells. Evidence for persistent virus production was monitored by the ELISA technique using an anti-HCV-specific antibody. Results obtained showed that all samples had an anti-HCV activity that increased by increasing concentration, and Boscia angustifalia had remarkable anti-HCV activity compared to Boscia senegalensis.

摘要

丙型肝炎病毒 (HCV) 是全球慢性肝病(包括慢性肝炎、肝硬化和肝细胞癌)的主要致病因子。HCV 的治疗已经从早期的干扰素单药治疗发展到目前使用直接作用抗病毒药物的全口服治疗方案。然而,抗病毒耐药性已成为接受直接作用抗病毒药物 (DAA) 治疗后慢性丙型肝炎治疗的一个关键问题,其复发率与其他慢性病毒感染相似。因此,治疗失败后的再治疗选择已成为关键问题。因此,本研究旨在探讨一种新的有前途的 HCV 治疗方法。在纳米医学领域,壳聚糖纳米粒是众所周知的递送系统,经常用作聚合物载体。半乳糖化壳聚糖纳米粒已广泛应用于 HCV 的治疗。在这项研究中,我们使用环保方法用抗坏血酸代替危险试剂对其进行了半乳糖化修饰,并将其负载了两种新测试的 Boscia 提取物,每种提取物有三个不同浓度。合成的壳聚糖纳米粒显示出两个分散峰,在 196±29nm 和 1.33±0.36μm 处,具有+3.3±0.4mV 的高稳定性,在 40.7mV 的范围内。发现 Boscia angustifalia 提取物的包封率为 46.58±1.33%,Boscia senegalensis 提取物的包封率为 9.77±0.33%。Boscia angustifalia 提取物从纳米粒中的释放约为 40%在酸性介质中 180 分钟后,在正常 pH 值下约为 60%。然而,Boscia senegalensis 提取物在酸性介质中的释放为 20%,在正常介质中为 56%24 小时后。使用建立的人肝癌细胞感染的体外系统对这两种新开发的复合材料进行了针对 HCV 的测试。使用抗 HCV 特异性抗体的 ELISA 技术监测持续病毒产生的证据。结果表明,所有样品均具有增加浓度时增强的抗 HCV 活性,并且 Boscia angustifalia 比 Boscia senegalensis 具有显著的抗 HCV 活性。

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