In many studies for chemoembolization of
hepatocellular carcinoma, the
Lipiodol emulsion preparation protocols, especially the mixing steps, were unclear or even unrevealed at all. However,
doxorubicin (DOX) release may depend on the composition and volume ratio (
Lipiodol to DOX
solution) of a
Lipiodol emulsion. Therefore, we conducted a preclinical study to compare in-vitro drug release and in-vivo pharmacokinetics of DOX from diverse
Lipiodol emulsions and
drug-eluting beads (DEBs) and to compare the
tumor response in a rabbit VX2
carcinoma model. DOX release profiles of four types of
Lipiodol emulsions with different media (
normal saline or Pamiray as an iodinated contrast medium), volume ratio (
Lipiodol to DOX
solution), and DEBs were investigated in-vitro. For the in-vivo study, 15 rabbits bearing VX2
carcinoma in the liver were treated with 4∶1 volume ratio
Lipiodol emulsion (group A), 1∶1 volume ratio
Lipiodol emulsion (group B), and DEBs (group C) chemoembolization. Blood and tissue sampling was conducted to evaluate DOX concentration in plasma and tissues, histological changes, and liver toxicity. The most stable
emulsion was formed with Pamiray (including DOX) at a 4∶1 volume ratio. The AUC value of group A was significantly lower than that of group B (p = 0.003) but comparable to that of group C (p = 0.071). The Cmax value of group A was significantly different compared with those of group B (p = 0.004) and C (p = 0.015). The tissue
drug concentration in group A was comparable to that in group C (p = 0.251). No viable
tumor was detected in rabbits of group A and B. In group C, viable
tumor less than 10% was seen in two of the five rabbits. There were no significant differences in liver
enzyme levels after the procedure. In conclusion, DOX release and pharmacokinetics of presented
emulsion systems depend substantially on their composition. Therefore,
Lipiodol emulsion type should be considered when interpreting data and designing new studies dealing with chemoembolization.