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

Purpose: To test the anticancer properties of the water-insoluble derivativ e of camptothecin, 9-nitrocamptothecin (9-NC) against human breast, colon a nd lung cancer xenografts in nude mice when administered in liposome aeroso l. Methods: The drug was formulated with dilauroylphosphatidylcholine and n ebulized in a particle size of 1.6 mu m +/- 2.0 mass median diameter to del iver doses of usually less than 200 mu g/kg daily, 5 days per week. 9-NC li posome aerosols were generated with a Aerotech II nebulizer (CIS-USA) flowi ng 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 wa s greatly reduced or tumors were undetectable after several weeks of treatm ent. Colon tumor was least responsive. 9-NC was better than the parent comp ound, camptothecin, also water-insoluble, tested by aerosol in a similar li posomal preparation. Equivalent doses of 9-NC liposome preparations adminis tered by mouth were substantially without effect while there was some effec t, but limited, of the liposome preparation given intramuscularly. Conclusi ons: 9-NC liposome aerosol was strikingly effective in the treatment of thr ee human cancer xenografts growing subcutaneously over the thorax in nude m ice at doses much smaller than those traditionally used in mice administere d by other routes.