Formulation of polyiodinated triglyceride analogues in a chylomicron remnant-like liver-selective delivery vehicle

A formulation methodology for the incorporation of polyiodinated triglyceride (ITG) analogues into a protein-free chylomicron remnant-like emulsion was developed to provide a vehicle for the selective hepatic delivery of these agents for contrast-enhanced X-ray computed tomography (CECT).

Triglyceride emulsions (10% w/v) were prepared at various processing pressures, temperatures and times with a Microfluidizer 110-S using different emulsion component proportions to establish processing and compositional parameters in order to afford stable ITG emulsions (ITG-LE) approaching 200 nm mean diameter.

Preliminary data indicated that with a formulation composed of 2.4% dioleoyl PC with a cholesterol:DOPC mole ratio of 0.4 emulsified at 14,700 psi, 35 degrees C for 10 min routinely afforded ITG-LE in the desired size range. The elimination of salt and amino acid from the bulk phase enhanced the stability of the ITG-LE. Incorporation of cholesterol into the monolayer was of critical importance in generating a stable emulsion near the targeted size, with a C:DOPC mole ratio of 0.4 producing a size minimum relative to higher or lower C:DOPC values.

The ITG analogues can be readily incorporated into stable remnant-like emulsions of relatively uniform particle size. Combination of the unique ITG contrast agent with the remnant-like delivery vehicle demonstrates a high degree of hepatic selectivity in biodistribution studies and offers significant potential for selective hepatic CECT.