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CardioVascular and Interventional Radiology
Published in: CardioVascular and Interventional Radiology 5/2018

01-05-2018 | Laboratory Investigation

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

Authors: 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 C. Larson

Published in: CardioVascular and Interventional Radiology | Issue 5/2018

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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.
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Metadata
Title
Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin
Authors
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 C. Larson
Publication date
01-05-2018
Publisher
Springer US
Published in
CardioVascular and Interventional Radiology / Issue 5/2018
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI
https://doi.org/10.1007/s00270-018-1899-y

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