STABILITY STUDIES ON CHEMOEMBOLIZATION MIXTURES - DIALYSIS STUDIES OF DOXORUBICIN AND LIPIODOL WITH AVITENE, GELFOAM, AND ANGIOSTAT

RATIONALE AND OBJECTIVES. Chemoembolization, using a combination of embolic and chemotherapeutic agents, appears to be an effective treatment for hepatocellular carcinoma. Although the postulated mechanism of effectiveness hinges on a prolonged drug delivery, increasing evidence suggests that embolization mixtures are not stable. The objective of this study was to investigate examples of these mixtures. METHODS. Dialysis techniques have been used to examine the pharmacokinetic properties of chemoembolization mixtures that contain doxorubicin, Lipiodol (Guerbet Products, Montreal, Quebec), and the embolizing agents Avitene (Alcon Laboratories Inc., Fort Worth, Texas), Gelfoam (Upjohn, Kalamazoo, MI), and Angiostat (Regional Therapeutic Inc., Pacific Palisades, CA). RESULTS. Lipiodol, Gelfoam, and Avitene, when combined with doxorubicin, had only a small effect on the diffusion of the drug when compared with the diffusion curve of doxorubicin alone. Gelfoam or Avitene produced a thrombus-like consistency when added to a doxorubicin/Lipiodol combination, and an additional decrease in the doxorubicin appearance rate was observed. However, after 6 hours, doxorubicin levels for these mixtures reached control values observed in 3 hours. Angiostat without Lipiodol produced a profound concentration-dependent decrease in the diffusion of doxorubicin. After 9 hours, only 23% of the doxorubicin had been released. CONCLUSION. The strong complexing ability of the embolic agent Angiostat may enable it to be a carrier for doxorubicin and surpass other mixtures currently employed for transcatheter chemoembolization.