Hepatic arterial injection chemotherapy for hepatocellular carcinoma with epirubicin aqueous solution as numerous vesicles in iodinated poppy-seed oil microdroplets: clinical application of water-in-oil-in-water emulsion prepared using a membrane emulsification technique.

Iodinated poppy-seed oil (IPSO) accumulates selectively in hepatocellular carcinoma (HCC) when injected into the hepatic artery. This virtue has been applied to the hepatic arterial injection chemotherapy for the disease. We invented a new water-in-oil-in-water emulsion (W/O/W), in which IPSO microdroplets, 70 micrometer in diameter, were suspended in physiological saline enclosing numerous vesicles of an aqueous solution of epirubicin with remarkable stability. After hepatic arterial injection, the microdroplets accumulated only in HCC tissue and remained in the tissue for more than 3 weeks affecting tumor cells. Efficacy of the W/O/W has been fully proved clinically; the 6-year cumulative survival rate for 24 patients bearing HCC nodules recurrent after hepatectomy, including even 12 patients with four or more nodules, though prognosis of these patients is recognized very poor, was 24%.