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Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice

机译:健康和慢性酒精喂养小鼠中阳离子脂质体暴露的肝毒性评估

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摘要

The utilisation of nanoparticles as the means of targeted delivery of therapeutics and/or imaging agents could greatly enhance the specific transport of biologically active payloads to target tissues while avoiding or reducing undesired side-effects. To allow for this to become a reality, the question of potential toxicological effects needs to be addressed. In the present investigation, a cationic liposome with prospective for medical applications was constructed and thoroughly assessed for any material-induced hepatic adverse effects in vivo − in healthy and alcoholic hepatic disease models and in vitro − (HepG2 cells). The data demonstrated that intravenous injection of liposomes did not cause any significant in vivo hepatic toxicity (inflammation, alterations in blood parameters, anti-oxidant depletion, acute phase response and histopathology) at doses of 200 μg per mouse in either healthy or chronically alcohol fed mice. Additionally, the in vitro material-induced adverse effects (cytotoxicity, inflammation or albumin secretion) were all also minimal. The data from this study demonstrated that the intravenous injection of cationic liposomes does not cause hepatic toxicity. This investigation is important as it investigates the toxicity of a nano-sized material in a model of alcoholic hepatic disease in vitro and in vivo. This is an area of research in the field of nanotoxicology that is currently almost entirely overlooked.
机译:纳米粒子作为治疗剂和/或成像剂的靶向递送的手段的使用可以极大地增强生物活性有效载荷向靶组织的特异性转运,同时避免或减少不希望的副作用。为了使这种情况成为现实,需要解决潜在的毒理学效应问题。在本研究中,构建了可用于医疗应用的阳离子脂质体,并在健康和酒精性肝病模型以及体外(HepG2细胞)中彻底评估了材料在体内引起的任何肝脏不良反应。数据表明,在健康或长期饮酒的情况下,以每只小鼠200μg的剂量静脉内注射脂质体不会引起任何明显的体内肝毒性(炎症,血液参数改变,抗氧化剂耗竭,急性期反应和组织病理学)老鼠。此外,体外材料诱导的副作用(细胞毒性,炎症或白蛋白分泌)也很小。这项研究的数据表明,静脉注射阳离子脂质体不会引起肝毒性。这项研究非常重要,因为它在酒精性肝病模型的体内和体外研究了纳米材料的毒性。这是纳米毒理学领域的研究领域,目前几乎被完全忽略了。

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