Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin

Frederic Deschamps*, Kathleen R. Harris, Laurence Moine, Weiguo Li, Lambros Tselikas, Thomas Isoardo, Robert J Lewandowski, Angelo Paci, Nicolas Huang, Thierry de Baere, Riad Salem, Andrew Christian Larson

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can adsorb at the water/oil interface to stabilize the emulsion (forming Pickering-emulsion). The purpose of this study was to compare the release profiles of oxaliplatin from Pickering-emulsion and Lipiodol-emulsion. Materials/Methods: Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin was selectively injected into left hepatic arteries of 18 rabbits bearing VX2 liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol-emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations. Results: Pickering-emulsion demonstrated a slow oxaliplatin release compared to Lipiodol-emulsion (1.5 ± 0.2 vs. 12.0 ± 6% at 1 h and 15.8 ± 3.0 vs. 85.3 ± 3.3% at 24 h) during in vitro comparison studies. For animal model studies, the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 ± 0.14 vs. 1.08 ± 0.41 ng/mL, p = 0.01 and AUC = 19.8 ± 5.9 vs. 31.8 ± 14.9, p = 0.03). This resulted in significantly lower oxaliplatin concentrations in tissues at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at 24 h (43.4 vs. 14.5, p = 0.04). Conclusion: Slow release of oxaliplatin from Pickering-emulsion results in a significant decrease in systemic drug exposure and higher ratio between tumor and left liver oxaliplatin concentration at 24 h.

Original languageEnglish (US)
Pages (from-to)781-788
Number of pages8
JournalCardiovascular and Interventional Radiology
Volume41
Issue number5
DOIs
StatePublished - May 1 2018

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oxaliplatin
Emulsions
Liver
Ethiodized Oil
glycolic acid

Keywords

  • Emulsion
  • Hepatocarcinoma
  • Lipiodol
  • Liver
  • Nanoparticles
  • Oxaliplatin

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Deschamps, Frederic ; Harris, Kathleen R. ; Moine, Laurence ; Li, Weiguo ; Tselikas, Lambros ; Isoardo, Thomas ; Lewandowski, Robert J ; Paci, Angelo ; Huang, Nicolas ; de Baere, Thierry ; Salem, Riad ; Larson, Andrew Christian. / Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin. In: Cardiovascular and Interventional Radiology. 2018 ; Vol. 41, No. 5. pp. 781-788.
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title = "Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin",
abstract = "Purpose: Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can adsorb at the water/oil interface to stabilize the emulsion (forming Pickering-emulsion). The purpose of this study was to compare the release profiles of oxaliplatin from Pickering-emulsion and Lipiodol-emulsion. Materials/Methods: Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin was selectively injected into left hepatic arteries of 18 rabbits bearing VX2 liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol-emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations. Results: Pickering-emulsion demonstrated a slow oxaliplatin release compared to Lipiodol-emulsion (1.5 ± 0.2 vs. 12.0 ± 6{\%} at 1 h and 15.8 ± 3.0 vs. 85.3 ± 3.3{\%} at 24 h) during in vitro comparison studies. For animal model studies, the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 ± 0.14 vs. 1.08 ± 0.41 ng/mL, p = 0.01 and AUC = 19.8 ± 5.9 vs. 31.8 ± 14.9, p = 0.03). This resulted in significantly lower oxaliplatin concentrations in tissues at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at 24 h (43.4 vs. 14.5, p = 0.04). Conclusion: Slow release of oxaliplatin from Pickering-emulsion results in a significant decrease in systemic drug exposure and higher ratio between tumor and left liver oxaliplatin concentration at 24 h.",
keywords = "Emulsion, Hepatocarcinoma, Lipiodol, Liver, Nanoparticles, Oxaliplatin",
author = "Frederic Deschamps and Harris, {Kathleen R.} and Laurence Moine and Weiguo Li and Lambros Tselikas and Thomas Isoardo and Lewandowski, {Robert J} and Angelo Paci and Nicolas Huang and {de Baere}, Thierry and Riad Salem and Larson, {Andrew Christian}",
year = "2018",
month = "5",
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doi = "10.1007/s00270-018-1899-y",
language = "English (US)",
volume = "41",
pages = "781--788",
journal = "CardioVascular and Interventional Radiology",
issn = "7415-5101",
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number = "5",

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Deschamps, F, Harris, KR, Moine, L, Li, W, Tselikas, L, Isoardo, T, Lewandowski, RJ, Paci, A, Huang, N, de Baere, T, Salem, R & Larson, AC 2018, 'Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin', Cardiovascular and Interventional Radiology, vol. 41, no. 5, pp. 781-788. https://doi.org/10.1007/s00270-018-1899-y

Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin. / Deschamps, Frederic; Harris, Kathleen R.; Moine, Laurence; Li, Weiguo; Tselikas, Lambros; Isoardo, Thomas; Lewandowski, Robert J; Paci, Angelo; Huang, Nicolas; de Baere, Thierry; Salem, Riad; Larson, Andrew Christian.

In: Cardiovascular and Interventional Radiology, Vol. 41, No. 5, 01.05.2018, p. 781-788.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin

AU - Deschamps, Frederic

AU - Harris, Kathleen R.

AU - Moine, Laurence

AU - Li, Weiguo

AU - Tselikas, Lambros

AU - Isoardo, Thomas

AU - Lewandowski, Robert J

AU - Paci, Angelo

AU - Huang, Nicolas

AU - de Baere, Thierry

AU - Salem, Riad

AU - Larson, Andrew Christian

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Purpose: Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can adsorb at the water/oil interface to stabilize the emulsion (forming Pickering-emulsion). The purpose of this study was to compare the release profiles of oxaliplatin from Pickering-emulsion and Lipiodol-emulsion. Materials/Methods: Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin was selectively injected into left hepatic arteries of 18 rabbits bearing VX2 liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol-emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations. Results: Pickering-emulsion demonstrated a slow oxaliplatin release compared to Lipiodol-emulsion (1.5 ± 0.2 vs. 12.0 ± 6% at 1 h and 15.8 ± 3.0 vs. 85.3 ± 3.3% at 24 h) during in vitro comparison studies. For animal model studies, the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 ± 0.14 vs. 1.08 ± 0.41 ng/mL, p = 0.01 and AUC = 19.8 ± 5.9 vs. 31.8 ± 14.9, p = 0.03). This resulted in significantly lower oxaliplatin concentrations in tissues at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at 24 h (43.4 vs. 14.5, p = 0.04). Conclusion: Slow release of oxaliplatin from Pickering-emulsion results in a significant decrease in systemic drug exposure and higher ratio between tumor and left liver oxaliplatin concentration at 24 h.

AB - Purpose: Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles can adsorb at the water/oil interface to stabilize the emulsion (forming Pickering-emulsion). The purpose of this study was to compare the release profiles of oxaliplatin from Pickering-emulsion and Lipiodol-emulsion. Materials/Methods: Pickering-emulsions and Lipiodol-emulsions were both formulated with oxaliplatin (5 mg/mL) and Lipiodol (water/oil ratio: 1/3). For Pickering-emulsion only, PLGA nanoparticles (15 mg/mL) were dissolved into oxaliplatin before formulation. In vitro release of oxaliplatin from both emulsions was evaluated. Then, oxaliplatin was selectively injected into left hepatic arteries of 18 rabbits bearing VX2 liver tumors using either 0.5 mL Pickering-emulsion (n = 10) or 0.5 mL Lipiodol-emulsion (n = 8). In each group, half of the rabbits were killed at 1 h and half at 24 h. Mass spectrometry was used to quantify drug pharmacokinetics in blood and resulting tissue (tumors, right, and left livers) oxaliplatin concentrations. Results: Pickering-emulsion demonstrated a slow oxaliplatin release compared to Lipiodol-emulsion (1.5 ± 0.2 vs. 12.0 ± 6% at 1 h and 15.8 ± 3.0 vs. 85.3 ± 3.3% at 24 h) during in vitro comparison studies. For animal model studies, the plasmatic peak (Cmax) and the area under the curve (AUC) were significantly lower with Pickering-emulsion compared to Lipiodol-emulsion (Cmax = 0.49 ± 0.14 vs. 1.08 ± 0.41 ng/mL, p = 0.01 and AUC = 19.8 ± 5.9 vs. 31.8 ± 14.9, p = 0.03). This resulted in significantly lower oxaliplatin concentrations in tissues at 1 h with Pickering-emulsion but higher ratio between tumor and left liver at 24 h (43.4 vs. 14.5, p = 0.04). Conclusion: Slow release of oxaliplatin from Pickering-emulsion results in a significant decrease in systemic drug exposure and higher ratio between tumor and left liver oxaliplatin concentration at 24 h.

KW - Emulsion

KW - Hepatocarcinoma

KW - Lipiodol

KW - Liver

KW - Nanoparticles

KW - Oxaliplatin

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