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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Longino
M A
MA
Department of Radiology, University of Michigan, Ann Arbor 48109-0662, USA.
Bakan
D A
DA
Weichert
J P
JP
Counsell
R E
RE
D002914:Chylomicrons / Q000737:chemistry*; D003287:Contrast Media / Q000008:administration & dosage / Q000138:chemical synthesis*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D008099:Liver / Q000378:metabolism*; D010316:Particle Size; D013499:Surface Properties; D013696:Temperature; D014280:Triglycerides / Q000008:administration & dosage / Q000138:chemical synthesis*
D002914:Chylomicrons; D003287:Contrast Media; D004655:Emulsions; D014280:Triglycerides