Cancer Chemotherapy and Pharmacology

, Volume 44, Issue 3, pp 177–186

Anticancer exffect of 9-nitrocamptothecin liposome aerosol on human cancer xenografts in nude mice

  • Vernon Knight
  • Nadezhda V. Koshkina
  • J. Clifford Waldrep
  • Beppino C. Giovanella
  • Brain E. Gilbert
ORIGINAL ARTICLE

DOI: 10.1007/s002800050965

Cite this article as:
Knight, V., Koshkina, N., Waldrep, J. et al. Cancer Chemother Pharmacol (1999) 44: 177. doi:10.1007/s002800050965

Abstract

Purpose: To test the anticancer properties of the water-insoluble derivative of camptothecin, 9-nitrocamptothecin (9-NC) against human breast, colon and lung cancer xenografts in nude mice when administered in liposome aerosol. Methods: The drug was formulated with dilauroylphosphatidylcholine and nebulized in a particle size of 1.6 μm ± 2.0 mass median diameter to deliver doses of usually less than 200 μg/kg daily, 5 days per week. 9-NC liposome aerosols were generated with a Aerotech II nebulizer (CIS-USA) flowing at 10 l/min from a compressed air source and delivered to mice in sealed plastic cages or in a nose-only exposure chamber. Results: Tumor growth was greatly reduced or tumors were undetectable after several weeks of treatment. Colon tumor was least responsive. 9-NC was better than the parent compound, camptothecin, also water-insoluble, tested by aerosol in a similar liposomal preparation. Equivalent doses of 9-NC liposome preparations administered by mouth were substantially without effect while there was some effect, but limited, of the liposome preparation given intramuscularly. Conclusions: 9-NC liposome aerosol was strikingly effective in the treatment of three human cancer xenografts growing subcutaneously over the thorax in nude mice at doses much smaller than those traditionally used in mice administered by other routes.

Key words AerosolLiposomeCancerCamptothecin9-Nitrocamptothecin

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Vernon Knight
    • 1
  • Nadezhda V. Koshkina
    • 1
  • J. Clifford Waldrep
    • 1
  • Beppino C. Giovanella
    • 2
  • Brain E. Gilbert
    • 3
  1. 1.Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Tel. +1-713-798-5155; Fax +1-713-798-3125US
  2. 2.Stehlin Foundation for Cancer Research at St. Joseph's Hospital, Houston, TX, USAUS
  3. 3.Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX, USAUS