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

Junjie Li, Diana Canseco, Yuzhu Wang, Gonçalo Vale, Jaideep Chaudhary, Arnida Anwar, Hamid Baniasadi, Noelle S. Williams, Purva Gopal, Patrick D. Sutphin, Jeffrey G. McDonald, William C. Putnam, Ian R Corbin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)273-283
Number of pages11
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume158
DOIs
StatePublished - Jan 1 2021

Keywords

  • Docosahexaenoic acid
  • Locoregional delivery
  • Low-density lipoprotein
  • Nanomedicine
  • Nanoparticle safety
  • Toxicity

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Assessing the safety of transarterial locoregional delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat liver'. Together they form a unique fingerprint.

Cite this