Stable lipiodolized emulsions for hepatoma targeting and treatment by transcatheter arterial chemoembolization

Abstract

We attempted to develop lipiodolized emulsions that remain in the tumour for a long period, release drug in a sustained release pattern, and thus improve the conventional treatment of hepatocellular carcinoma (HCC) [1]. Polyoxyethylene derivatives of hydrogenated castor oil (HCO) were the most suitable emulsifiers in stabilizing emulsions containing Lipiodol(R) as an oil phase. The length of ethylene oxide coupled to HCO rather than the hydrophilic-lipophilic balance (HLB) values was an important factor in preparing stable emulsions and in achieving sustained-release characteristics. When distilled water was replaced with Iopamiro(R), a heavy water soluble contrast medium with a specific gravity of 1.335, more stable lipiodolized emulsions with longer sustained release behaviour could be prepared with smaller amount of HCO. To study the in vivo stability of the w/o Lipiodol emulsion and the sustained-release characteristics of doxorubicin from the emulsion, the pharmacokinetic study was performed with normal dogs using transcatheter arterial chemoembolization technique. The area under the plasma concentration-time curve for the first eight hours (AUC(0-8)) and AUC(total) values of the stabilized emulsion were three to four times higher than those of the coarse emulsion prepared lacking HCO 60. From the in vitro and in vivo studies, Lipiodol based water in oil emulsion with HCO 60 containing doxorubicin showed higher stability and released doxorubicin in a sustained fashion. (C) 1998 Elsevier Science B.V.