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

  • Laboratory Investigation
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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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Acknowledgements

The authors thank Woo-Ram Park, Xiaoke Huang, Soojeong Cho, and Lionel Mercier for their previous technical support. Metal analysis was performed at the Northwestern University Quantitative Bio-element Imaging Center generously supported by NASA Ames Research Center Grant NNA04CC36G.

Funding

This study was supported by NIH funding source (R01CA181658).

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Authors and Affiliations

  1. Département de radiologie Interventionnelle, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, 94805, Villejuif, France

    Frederic Deschamps, Lambros Tselikas & Thierry de Baere

  2. Department of Radiology, Northwestern University, Chicago, USA

    Kathleen R. Harris, Weiguo Li, Robert J. Lewandowski, Riad Salem & Andrew C. Larson

  3. Institut Galien, CNRS, UMR 8612, Faculté de Pharmacie, Université Paris-Saclay, Châtenay-Malabry, France

    Laurence Moine, Thomas Isoardo & Nicolas Huang

  4. CNRS, UMR 8203, Université Paris-Saclay, Villejuif, France

    Frederic Deschamps & Angelo Paci

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  1. Frederic Deschamps
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  2. Kathleen R. Harris
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Correspondence to Frederic Deschamps.

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Deschamps, F., Harris, K.R., Moine, L. et al. Pickering-Emulsion for Liver Trans-Arterial Chemo-Embolization with Oxaliplatin. Cardiovasc Intervent Radiol 41, 781–788 (2018). https://doi.org/10.1007/s00270-018-1899-y

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  • DOI: https://doi.org/10.1007/s00270-018-1899-y

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