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Research ArticleArticle

Size of Lipid Microdroplets Effects Results of Hepatic Arterial Chemotherapy with an Anticancer Agent in Water-in-Oil-in-Water Emulsion to Hepatocellular Carcinoma

Shushi Higashi, Naoto Tabata, Kazu-Hiro Kondo, Yorio Maeda, Masataka Shimizu, Tadao Nakashima and Toshiaki Setoguchi
Journal of Pharmacology and Experimental Therapeutics May 1999, 289 (2) 816-819;
Shushi Higashi
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Naoto Tabata
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Kazu-Hiro Kondo
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Yorio Maeda
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Masataka Shimizu
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Tadao Nakashima
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Toshiaki Setoguchi
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Abstract

We have initially prepared a new drug delivery system for hepatocellular carcinoma (HCC). Using sonication and a detergent, iodinated poppy seed oil (IPSO) can be mixed with an aqueous solution of epirubicin to make a water-in-oil emulsion. The water-in-oil emulsion is further passed through a microporous glass membrane and split into saline to make a long-term inseparable water-in-oil-in-water emulsion (W/O/W) that consists of IPSO microdroplets. To investigate the effect of the size of IPSO microdroplets on the efficacy of injection chemotherapy with W/O/W in patients with HCC, 32 HCC patients were randomly assigned and treated with W/O/W of small IPSO microdroplets (30 μm in diameter) containing 60 mg of epirubicin (n = 16, group A) or W/O/W of large IPSO microdroplets (70 μm) containing the same amounts of epirubicin (n = 16, group B). Effects were assessed by measuring the percentage of decline of the α-fetoprotein (AFP) level in a week from the AFP level immediately before the treatment. The decline was significantly larger in group B (50.5 ± 19.8, mean ± S.D.) compared with group A (18.9 ± 33.1;p < .005). The size of IPSO microdroplets injected into the hepatic artery determines the decrease of serum AFP levels of the patients with HCC.

Footnotes

  • Send reprint requests to: Dr. Shushi Higashi, M.D., Ph.D., Department of Surgery I, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, Miyazaki, 889-1692, Japan.

  • Abbreviations:
    IPSO
    ethyl esters of iodinated fatty acids obtained by hydrolysis of poppy-seed oil
    HCC
    hepatocellular carcinoma
    W/O
    water-in-oil emulsion
    W/O/W
    water-in-oil-in-water emulsion
    polyoxyethylene 60 stearate
    hydrogenated castor oil treated with ethylene oxide (1:60, molar ratio)
    AFP
    α-fetoprotein
    sGOT
    glutamic oxaloacetic transaminase
    sGPT
    glutamic pyruvic transaminase
    LDH
    lactate dehydrogenase
    • Received July 10, 1998.
    • Accepted December 14, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 2
1 May 1999
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Research ArticleArticle

Size of Lipid Microdroplets Effects Results of Hepatic Arterial Chemotherapy with an Anticancer Agent in Water-in-Oil-in-Water Emulsion to Hepatocellular Carcinoma

Shushi Higashi, Naoto Tabata, Kazu-Hiro Kondo, Yorio Maeda, Masataka Shimizu, Tadao Nakashima and Toshiaki Setoguchi
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 816-819;

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Research ArticleArticle

Size of Lipid Microdroplets Effects Results of Hepatic Arterial Chemotherapy with an Anticancer Agent in Water-in-Oil-in-Water Emulsion to Hepatocellular Carcinoma

Shushi Higashi, Naoto Tabata, Kazu-Hiro Kondo, Yorio Maeda, Masataka Shimizu, Tadao Nakashima and Toshiaki Setoguchi
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 816-819;
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