Comparison of Lipiodol Water-in-Oil-in-Water Emulsion and Oil-in-Water Emulsion: Acute Toxicity and Deposition in Liver after Hepatic Arterial Administration in Rats

Abstract

Lipiodol is an oily contrast medium widely used as an embolizing material for transcatheter arterial embolization (TAE) therapy, an effective method for treating unresectable hepatocellular carcinoma. We investigated the acute toxicity and deposition in the liver of lipiodol water‐in‐oil‐in‐water (w/o/w) emulsion encapsulating epirubicin hydrochloride after hepatic arterial administration to rats, and compared results with those of the oil‐in‐water (o/w) emulsion conventionally used for TAE therapy. Deposition was detected by means of an X‐ray CT scanner. It was, therefore, suggested that the dose of the emulsions would be controllable by monitoring them during the surgical operation. The concentration of epirubicin hydrochloride in the liver was increased and its residence was prolonged by encapsulating it in the w/o/w emulsion membranes. The toxic effects of epirubicin hydrochloride and lipiodol on the normal hepatic cells were reduced, resulting in a decrease in both glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activity. Consequently, an enhanced therapeutic effect of w/o/w emulsion would be expected compared with the conventional o/w emulsion, owing to the sustained release of the agent and the targeting property of lipiodol to the malignant cells. It was concluded that the w/o/w emulsion is a suitable formulation for chemoembolization therapy.