Parameters for Stable Water-in-Oil Lipiodol Emulsion for Liver Trans-Arterial Chemo-Eembolization

Cardiovasc Intervent Radiol. 2017 Dec;40(12):1927-1932. doi: 10.1007/s00270-017-1763-5. Epub 2017 Aug 2.

Abstract

Purpose: Water-in-oil type and stability are important properties for Lipiodol emulsions during conventional trans-arterial chemo-embolization. Our purpose is to evaluate the influence of 3 technical parameters on those properties.

Materials and methods: The Lipiodol emulsions have been formulated by repetitive back-and-forth pumping of two 10-ml syringes through a 3-way stopcock. Three parameters were compared: Lipiodol/doxorubicin ratio (2/1 vs. 3/1), doxorubicin concentration (10 vs. 20 mg/ml) and speed of incorporation of doxorubicin in Lipiodol (bolus vs. incremental vs. continuous). The percentage of water-in-oil emulsion obtained and the duration until complete coalescence (stability) for water-in-oil emulsions were, respectively, evaluated with the drop-test and static light scattering technique (Turbiscan).

Results: Among the 48 emulsions formulated, 32 emulsions (67%) were water-in-oil. The percentage of water-in-oil emulsions obtained was significantly higher for incremental (94%) and for continuous (100%) injections compared to bolus injection (6%) of doxorubicin. Emulsion type was neither influenced by Lipiodol/doxorubicin ratio nor by doxorubicin concentration. The mean stability of water-in-oil emulsions was 215 ± 257 min. The emulsions stability was significantly longer when formulated using continuous compared to incremental injection (326 ± 309 vs. 96 ± 101 min, p = 0.018) and using 3/1 compared to 2/1 ratio of Lipiodol/doxorubicin (372 ± 276 vs. 47 ± 43 min, p = <0.0001). Stability was not influenced by the doxorubicin concentration.

Conclusion: The continuous and incremental injections of doxorubicin in the Lipiodol result in highly predictable water-in-oil emulsion type. It also demonstrates a significant increase in stability compared to bolus injection. Higher ratio of Lipiodol/doxorubicin is a critical parameter for emulsion stability too.

Keywords: Chemotherapy; Emulsions; Hepatocarcinoma; Lipiodol; Liver.

MeSH terms

  • Antibiotics, Antineoplastic / chemistry*
  • Chemoembolization, Therapeutic*
  • Doxorubicin / chemistry*
  • Emulsions
  • Ethiodized Oil / chemistry*
  • Liver Neoplasms*
  • Water

Substances

  • Antibiotics, Antineoplastic
  • Emulsions
  • Water
  • Ethiodized Oil
  • Doxorubicin