Distribution of camptothecin after delivery as a liposome aerosol or following intramuscular injection in mice

Purpose: The plant alkaloid camptothecin (CPT) has shown significant antitu mor activity against a wide variety of human tumors xenografted in nude mic e. In previous studies we have found that administration of dilauroylphosph atidylcholine (DLPC) liposome aerosols containing 9-nitrocamptothecin (9-NC ) inhibits the growth of human breast, colon and lung cancer xenografts. Th e purpose of this study was to analyze the pharmacokinetics and tissue dist ribution of inhaled CPT formulated in DLPC liposomes. Methods: C57BL/6 mice with subcutaneous Lewis lung carcinoma, Swiss nu/nu mice with human lung c arcinoma xenografts and BALB/c mice without tumors were used for pharmacoki netic studies of CPT administered as a liposome aerosol and BALB/c mice wer e given CPT intramuscularly. Results: After 30 min inhalation of CPT liposo me aerosol, drug was deposited in the lungs (310 ng/g) and was followed pro mptly by the appearance of high concentrations in the liver (192 ng/g) and with lesser amounts appearing in other organs. Drug concentration in the br ain was 61 ng/g. After intramuscular injection of CPT dissolved in DMSO, dr ug was released from the site of injection very slowly and accumulated main ly in the liver (136 ng/g. Only trace amounts appeared in the lungs (2-4 ng /g). These results demonstrate a prompt pulmonary and later systemic distri bution of CPT following liposome aerosol administration. Conclusions: The s ubstantial concentrations of CPT in lungs and other organs following inhala tion of liposome aerosol suggest the possible benefit of it and of its more active derivative, 9-NC, in the treatment of lung, liver, kidney and brain cancer in humans.