STABLE LIPIODOLIZED EMULSIONS FOR HEPATOMA TARGETING AND TREATMENT BYTRANSCATHETER ARTERIAL CHEMOEMBOLIZATION

We attempted to develop lipiodolized emulsions that remain in the tumo ur 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 containin g Lipiodol(R) as an oil phase. The length of ethylene oxide coupled to HCO rather than the hydrophilic-lipophilic balance (HLB) values was a n important factor in preparing stable emulsions and in achieving sust ained-release characteristics. When distilled water was replaced with Iopamiro(R), a heavy water soluble contrast medium with a specific gra vity of 1.335, more stable lipiodolized emulsions with longer sustaine d release behaviour could be prepared with smaller amount of HCO. To s tudy the in vivo stability of the w/o Lipiodol emulsion and the sustai ned-release characteristics of doxorubicin from the emulsion, the phar macokinetic study was performed with normal dogs using transcatheter a rterial chemoembolization technique. The area under the plasma concent ration-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 vit ro and in vivo studies, Lipiodol based water in oil emulsion with HCO 60 containing doxorubicin showed higher stability and released doxorub icin in a sustained fashion. (C) 1998 Elsevier Science B.V.