Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads

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 Lipio...

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Autores principales: Choi, Jin Woo, Cho, Hyun-Jong, Park, Ju-Hwan, Baek, Song Yi, Chung, Jin Wook, Kim, Dae-Duk, Kim, Hyo-Cheol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281073/
https://www.ncbi.nlm.nih.gov/pubmed/25551760
http://dx.doi.org/10.1371/journal.pone.0115898
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author Choi, Jin Woo
Cho, Hyun-Jong
Park, Ju-Hwan
Baek, Song Yi
Chung, Jin Wook
Kim, Dae-Duk
Kim, Hyo-Cheol
author_facet Choi, Jin Woo
Cho, Hyun-Jong
Park, Ju-Hwan
Baek, Song Yi
Chung, Jin Wook
Kim, Dae-Duk
Kim, Hyo-Cheol
author_sort Choi, Jin Woo
collection PubMed
description 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 C(max) 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.
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spelling pubmed-42810732015-01-07 Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads Choi, Jin Woo Cho, Hyun-Jong Park, Ju-Hwan Baek, Song Yi Chung, Jin Wook Kim, Dae-Duk Kim, Hyo-Cheol PLoS One Research Article 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 C(max) 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. Public Library of Science 2014-12-31 /pmc/articles/PMC4281073/ /pubmed/25551760 http://dx.doi.org/10.1371/journal.pone.0115898 Text en © 2014 Choi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Choi, Jin Woo
Cho, Hyun-Jong
Park, Ju-Hwan
Baek, Song Yi
Chung, Jin Wook
Kim, Dae-Duk
Kim, Hyo-Cheol
Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads
title Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads
title_full Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads
title_fullStr Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads
title_full_unstemmed Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads
title_short Comparison of Drug Release and Pharmacokinetics after Transarterial Chemoembolization Using Diverse Lipiodol Emulsions and Drug-Eluting Beads
title_sort comparison of drug release and pharmacokinetics after transarterial chemoembolization using diverse lipiodol emulsions and drug-eluting beads
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281073/
https://www.ncbi.nlm.nih.gov/pubmed/25551760
http://dx.doi.org/10.1371/journal.pone.0115898
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