Physicochemical Characterization of a Synthetic Lipid Emulsion for Hepatocyte-Selective Delivery of Lipophilic Compounds: Application to Polyiodinated Triglycerides as Contrast Agents for Computed Tomography

Abstract

A synthetic lipid emulsion (LE) has been developed with physicochemical properties that closely resemble those of a specific class of naturally-occurring lipoproteins known as chylomicron remnants. The formulation has the potential to serve as a hepatocyte-selective delivery system for any lipophilic or amphipathic compounds that can be associated with the internal lipid phase of the emulsion. In the present studies, a lipophilic polyiodinated triglyceride (ITG) was successfully incorporated into the delivery vehicle to form a stable chylomicron-remnant-like emulsion capable of localizing material to the liver following intravenous injection. The preferred ITG-LE formulation was shown to have a mean particle diameter of less than 200 nm and a particle size stability profile in excess of 12 months. The viscosity, pH, and osmolality of the formulation also appeared favorable for safe and convenient intravenous injection. The particle size profile, chemical properties, and high degree of incorporation of ITG into the emulsion suggest that the ITG-LE formulation holds substantial promise as a hepatocyte-selective imaging agent for computed tomography of the liver. Biodistribution, elimination, and computed tomography (CT) imaging results in animals corroborated the hepatocyte-selective nature of the ITG-LE formulation.

MicroCT Liver Contrast Agent Enhancement Over Time, Dose, and Mouse Strain

“…These receptors are widely distributed, including the liver, spleen, and macrophages [12]. Others have also noted a high splenic uptake of liver-specific iodinated contrast agents and hypothesized it was due to the reticuloendothelial system, part of the immune system, consisting primarily of monocytes and macrophages [13].…”

Noninvasive monitoring of a murine model of metastatic pheochromocytoma: A comparison of contrast‐enhanced microCT and nonenhanced MRI

“…Fenestra™LC used in this study has been described in detail previously (13,14). Ten nude mice were used to determine the contrast ratio (CR) and contrast-to-nose ratio (CNR), and two acquisitions were obtained.…”

Time-Course of Contrast Enhancement in Spleen and Liver with Exia 160, Fenestra LC, and VC

“…They are highly biocompatible, and they reduce systemic toxic effects by entrapping bioactive agents [14]. Different types of liposomal contrast (liposomal iodixanol, iodinated triglyceride (ITG), iodinated triglyceride lipid emulsion (ITG-LE), and iodinated triglyceride polyethylene glycol (ITG-PEG)) have been developed and analyzed in previous articles [15][16][17][18][19][20][21].…”