Organ-selective action of an antitumor drug: pharmacologic studies of liposome-encapsulated beta-cytosine arabinoside administered via the respiratory system of the rat.

beta-Cytosine arabinoside (Ara-C) in free and liposome encapsulated form was administered to Wistar rats by intratracheal institution. Free [3H]Ara-C administered in this manner rapidly left the lung and entered the systemic circulation. Liposome-encapsulated [3H]Ara-C persisted in the lung for a long period, with little redistribution to other tissues. Liposomes administered via the trachea became widely distributed throughout the lung air spaces, as evidenced by the histochemical localization of liposomes containing horse-radish peroxidase. Free Ara-C (5 mg/kg) administered into the trachea effectively suppressed macromolecular incorporation of [14C]thymidine ([14C]dThd) in the bone marrow and gut as well as in the lung. Liposome-encapsulated Ara-C (5 mg/kg) effectively suppressed macromolecular incorporation of [14C]dThd in the lung but had little effect on this process in the gut and bone marrow. Our results suggest that liposome-encapsulated Ara-C may be able to produce a local pharmacologic effect within the lung without producing adverse side effects in other tissues. This observation may be relevant to the chemotherapy of pulmonary metastases.