ORGAN-SELECTIVE ACTION OF AN ANTI-TUMOR 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 instillation. 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 through-out the lung air spaces, as evidenced by the histochemical localization of liposomes containing horseradish 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. 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 human pulmonary metastases.