Controlled delivery of an antitumor drug: localized action of liposome encapsulated cytosine arabinoside administered via the respiratory system.

Cytosine arabinoside in free or liposome encapsulated form was administered to the lungs of rats via intratracheal instillation. The free drug rapidly left the lung (T 1/2 = 40 min), while the encapsulated drug remained in the lung for a prolonged period (T 1/2 = 8 hr). Free cytosine arabinoside effectively inhibited DNA synthesis (measured by [14C]thymidine incorporation) in the intestine and bone marrow as well as in the lung. By contrast, liposome-encapsulated drug effectively inhibited DNA synthesis in the lung, but similar doses failed to inhibit DNA synthesis in other tissues. The metabolism of free and encapsulated drug were similar in that the same products resulted, namely the inactive catabolite uracil-beta-D-arabinofuranoside and the phosphorylated anabolites of cytoside arabinoside. These results suggest that the action of an antitumor drug can be confined to a single organ through the use of a liposomal drug delivery system.