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评估载脂蛋白 E 缺陷型大鼠低密度脂蛋白二十二碳六烯酸纳米粒经肝动脉区域性给药的安全性。

Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver.

机构信息

Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

Department of Pharmaceutical Sciences and Department of Pharmacy Practice within the Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, TX 75235, USA.

出版信息

Eur J Pharm Biopharm. 2021 Jan;158:273-283. doi: 10.1016/j.ejpb.2020.10.018. Epub 2020 Nov 24.

DOI:10.1016/j.ejpb.2020.10.018
PMID:33242579
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8121338/
Abstract

Hepatic-arterial infusion (HAI) of low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) (LDL-DHA) has been shown in a rat hepatoma model to be a promising treatment for hepatocellular carcinoma. To date, little is known regarding the safety of HAI of LDL-DHA to the liver. Therefore, we aimed to investigate the deposition, metabolism and safety of HAI of LDL-DHA (2, 4 or 8 mg/kg) in the rat. Following HAI, fluorescent labeled LDL nanoparticles displayed a biexponential plasma concentration time curve as the particles were rapidly extracted by the liver. Overall, increasing doses of HAI of LDL-DHA was well tolerated in the rat. Body weight, plasma biochemistry and histology were all unremarkable and molecular markers of inflammation did not increase with treatment. Lipidomics analyses showed that LDL-DHA was preferentially oxidized to the anti-inflammatory mediator, protectin DX. We conclude that HAI of LDL-DHA nanoparticles is not only safe, but provides potential hepatoprotective benefits.

摘要

载脂蛋白 B 衍生的富含二十二碳六烯酸的低密度脂蛋白纳米颗粒经肝动脉输注治疗肝细胞癌的安全性研究

载脂蛋白 B 衍生的富含二十二碳六烯酸的低密度脂蛋白纳米颗粒（LDL-DHA）经肝动脉输注（HAI）治疗大鼠肝癌模型已显示出巨大的应用潜力。迄今为止，关于 LDL-DHA 的 HAI 对肝脏的安全性知之甚少。因此，我们旨在研究 LDL-DHA（2、4 或 8mg/kg）的 HAI 在大鼠体内的沉积、代谢和安全性。HAI 后，荧光标记的 LDL 纳米颗粒显示出双指数血浆浓度时间曲线，因为这些颗粒被肝脏迅速提取。总的来说，大鼠能很好地耐受不同剂量的 LDL-DHA 的 HAI。体重、血浆生物化学和组织学均无明显异常，且炎症的分子标志物也未随治疗而增加。脂质组学分析表明，LDL-DHA 优先被氧化为抗炎介质，保护素 DX。我们的结论是，LDL-DHA 纳米颗粒的 HAI 不仅安全，而且具有潜在的肝脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f0/8121338/e83f08abd341/nihms-1693656-f0007.jpg
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