Evaluation of water in oil and microsphere in oil emulsions as a specific delivery system of 5-fluorouracil into lymphatics.

Abstract

The efficiency of water in oil (W/O) and gelatin microsphere in oil (S/O) emulsion as a drug delivery system for delivering 5-fluorouracil (5-FU) specifically into lymphatics was evaluated in the rat. Following intragastric and i.m. injection in the forms of emulsions and aqueous solution, radioactivities of 3H-labeled 5-FU or its antibacterial activities in plasma, regional lymph nodes, thoracic lymph and the injection site were compared with those following i.v. injection. W/O and S/O emulsion predominantly increased the area under the concentration-time curve (AUC) of 5-FU in the regional lymph nodes and cumulative amount transported into thoracic lymph. A pronounced retardation of release of 5-FU and decrease of peak plasma concentration were also obtained following injection of these emulsions. A local injection of 5-FU with emulsions was confirmed to be considerably advantageous from the viewpoint of metabolic inactivation. These results suggest the superiority of W/O and S/O emulsion in a surgical adjuvant cancer chemotherapy by satisfying many of the criteria of an ideal drug delivery system. S/O emulsion exhibited the best efficacy throughout present examinations.