Nv. Koshkina et al., Distribution of camptothecin after delivery as a liposome aerosol or following intramuscular injection in mice, CANC CHEMOT, 44(3), 1999, pp. 187-192
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.