Bleomycin-Lipiodol Suspension for Intralymphatic Administration in Esophageal Cancer

Bleomycin (BLM)-Lipiodol suspension was prepared for intralymphatic chemotherapy of esophageal cancer. The suspension was prepared by dispersing BLM directly into lipid contrast medium, Lipodol. One half of the suspension was then ultrasonicated. The dispersibility, physico-chemical stability and releasability of BLM in sonicated suspension were compared in vitro with those of non-sonicated suspension. The clinical availability of sonicated suspension was also evaluated. BLM in sonicated suspension was kept dispersed more uniformly as smaller particles than that in non-sonicated suspension for at least 3 days after the preparation. BLM in these suspensions was fairly stable under storage at room temperature for 3 days, showing the residual intact drug contents at higher than 96%. The in vitro release of BLM was so slow as to show only about 15 and 20% released from both suspensions in 60min at 50 and 100rpm, respectively. Under any rotatory condition, the release of BLM was or tended to be rather sustained from the sonicated suspension. After intralymphatic injection of the sonicated suspension, BLM was transported into regional lymph nodes and was detected at a considerable level ranging from 0.1 to 23.0 μg/g. BLM levels in thoracic and abdominal lymph nodes tended to be higher than those in cervical lymph nodes. These findings suggest that BLM-Lipiodol suspension may be a useful preparation for the targeting chemotherapy to esophageal cancer.