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12 Prevention of contrast-media induced renovascular toxicity using lipid nanoparticle encapsulation
  1. Rachel Donaghey,
  2. Alexander B Mullen,
  3. Paul A Coats
  1. Strathclyde’s Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Scotland, UK

Abstract

Introduction The primary goal of conventional lipid nanoparticles (LiNPs) is to target and release drugs at the site of disease. In comparison, this research aims to minimise drug interactions by entrapping the nephrotoxic contrast agent, iohexol (IOX), within protective particles. Susceptible patients, such as those with diabetes, suffer from pre-existing vascular dysfunction which is exacerbated by IOX.1 Mechanisms of IOX-associated toxicity are unknown, therefore, cell-based assays will be used to examine toxicity and whether it may be prevented through LiNP encapsulation.

Method Human umbilical vein endothelial cells (HUVEC), vascular (VSMC) and kidney cells (HEK-293) and were treated with IOX or IOX-encapsulated LiNPs (n=3). A metabolic indicator assay were used to determine metabolic activity after treatment proliferation and toxicity. Cell counting and a dye exclusion assay were used to confirm toxicity.

Results Resazurin experiments showed a significant reduction in metabolic activity after 2 hour IOX incubation resulting in a 54%, 15% and 52% reduction in HUVEC, VSMC and HEK-293 metabolic activity respectively. These results were confirmed through cell counting analysis. Encapsulation of IOX within LiNPs was found to prevent IOX-associated renal toxicity as metabolic activity was comparable to non-treated cells (129%) (p<0.05).

Conclusions Treatment of HEK-293 and VSMCs with IOX led to a reduction in viable cells and an increase in toxicity which was mainly influenced by concentration rather than time. Encapsulation of IOX within LiNPs was found to prevent toxicity in vitro. Future work will be carried out to determine mechanisms behind contrast agent-associated toxicity with a focus on ex vivo kidney perfusion and vascular contractile experiments.

Reference

  1. . Weisberg, et al. Kidney Int 1994;45:259–265.

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