Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads
Open Access
- 31 December 2014
- journal article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 9 (12), e115898
- https://doi.org/10.1371/journal.pone.0115898
Abstract
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.This publication has 28 references indexed in Scilit:
- Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: A reviewCritical Reviews in Oncology/Hematology, 2013
- Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinomaJournal of Hepatology, 2012
- Transcatheter Treatment of Hepatocellular Carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): Technical RecommendationsCardioVascular and Interventional Radiology, 2011
- Management of hepatocellular carcinoma: An updateJournal of Hepatology, 2011
- Transarterial Chemoembolization Can Be Safely Performed in Patients with Hepatocellular Carcinoma Invading the Main Portal Vein and May Improve the Overall SurvivalRadiology, 2011
- Prospective Randomized Study of Doxorubicin-Eluting-Bead Embolization in the Treatment of Hepatocellular Carcinoma: Results of the PRECISION V StudyCardioVascular and Interventional Radiology, 2009
- The Current Practice of Transarterial Chemoembolization for the Treatment of Hepatocellular CarcinomaKorean Journal of Radiology, 2009
- New Intra-arterial Drug Delivery System for the Treatment of Liver Cancer: Preclinical Assessment in a Rabbit Model of Liver CancerClinical Cancer Research, 2006
- DC Bead: In Vitro Characterization of a Drug-delivery Device for Transarterial ChemoembolizationJournal of Vascular and Interventional Radiology, 2006
- Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary reportEuropean Journal of Cancer and Clinical Oncology, 1983