Parameters for Stable Water-in-Oil Lipiodol Emulsion for Liver Trans-Arterial Chemo-Eembolization
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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).
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.
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.
KeywordsEmulsions Lipiodol Chemotherapy Liver Hepatocarcinoma
The authors thank Miss Fanny E. Hory for her gracious editing of this manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors declare they have no conflict of interest.
Incremental injection of 1 ml of doxorubicin in 3 ml of Lipiodol using 2 consecutive aliquots of 0.5 ml, each followed by 35 back-and-forth through the 3-way stopcock during 35 s
Continuous injection of doxorubicin (1 ml during 1 min) in 3 ml Lipiodol using an electric syringe pump during 60 back-and-forth through the 3-way stopcock, followed by 10 additional back-and-forth after the end of the injection
Drop-test of 3 emulsions formulated with a doxorubicin concentration of 20 mg/ml and 3/1 Lipiodol/doxorubicin ratio but 3 different speeds of incorporation of doxorubicin in Lipiodol. The bolus injection (on the left) resulted in an oil-in-water emulsion (no miscibility of the droplet in the Lipiodol), whereas the incremental injection (in the middle) and the continuous injection (on the right) resulted in a water-in-oil emulsion (miscibility of the droplets in the Lipiodol)
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