| Literature DB >> 33242579 |
Junjie Li1, Diana Canseco2, Yuzhu Wang3, Gonçalo Vale4, Jaideep Chaudhary1, Arnida Anwar1, Hamid Baniasadi5, Noelle S Williams5, Purva Gopal6, Patrick D Sutphin7, Jeffrey G McDonald4, William C Putnam2, Ian R Corbin8.
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.Entities:
Keywords: Docosahexaenoic acid; Locoregional delivery; Low-density lipoprotein; Nanomedicine; Nanoparticle safety; Toxicity
Mesh：
Substances：
Year: 2020 PMID： 33242579 PMCID： PMC8121338 DOI： 10.1016/j.ejpb.2020.10.018
Source DB: PubMed Journal: Eur J Pharm Biopharm ISSN： 0939-6411 Impact factor: 5.571