Small particle liposome aerosols for delivery of anti-cancer drugs

Abstract

The small particle liposome or lipid complex aerosol compounds and methods of treatment of the present invention involve lipid- or water soluble anti-cancer drugs incorporated into liposomes or other lipid complexes. The liposomes and complexes are administered in aqueous dispersions from a jet nebulizer to the respiratory tract of an individual. Various anti-cancer drugs may be used, including 20-S-Camptothecin, 9-Nitro-camptothecin, 9-Amino-camptothecin, 10,11 -methylenedioxy-camptothecin and taxol or its derivatives. Administration of these drugs by inhalation provides faster and more efficient absorption of the anticancer drug than does intramuscular administration or oral administration.

What is claimed is:  
     
         1 . A method for treating cancer, comprising the step of delivering, via small particle aerosol, aqueous dispersions of anti-cancer drugs in liposomes or lipid complexes to the respiratory tract of an individual in need of such treatment.  
     
     
         2 . The method of  claim 1 , wherein said anti-cancer drug is selected from the group consisting of 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, 10,11-methylenedioxy-camptothecin, taxol, taxol-A, mitotane, methotrexate, mercaptopurine, lomustine, interferon, 5-fluorouracil and etopiside.  
     
     
         3 . The method of  claim 2 , wherein said anti-cancer drug is selected from the group consisting of 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, 10,11-methylenedioxy-camptothecin and taxol.  
     
     
         4 . The method of  claim 1 , wherein said delivering step is performed by a jet nebulizer.  
     
     
         5 . The method of  claim 4 , wherein said liposomes are sheared to a diameter of less than 500 nm by said jet nebulizer.  
     
     
         6 . The method of  claim 1 , wherein a final concentration of said anticancer drug in said liposomes or lipid complexes is no greater than 5.0 mg/ml.  
     
     
         7 . The method of  claim 6 , wherein a final concentration of said anticancer drug in said liposomes or lipid complexes is no greater than 1.0 mg/ml.  
     
     
         8 . A liposome or lipid complex for delivery of anticancer drugs via small particle aerosol, wherein a ratio of anticancer drug to lipid is about 1:1 to about 1:200 wt:wt.  
     
     
         9 . The liposome or lipid complex of  claim 8 , wherein a ratio of anticancer drug to lipid is about 1:10 to about 1:100 wt:wt.  
     
     
         10 . The liposome or lipid complex of  claim 9 , wherein a ratio of anticancer drug to lipid is about 1:10 to about 1:50 wt:wt.  
     
     
         11 . The liposome or lipid complex of  claim 8 , wherein said anticancer drug is camptothecin or a derivative of camptothecin, said lipid is dilauroylphosphatidylcholine, and said ratio is about 1:10 to about 1:50.  
     
     
         12 . The liposome or lipid complex of  claim 8 , wherein said anticancer drug is taxol or its derivatives, said lipid is dilauroylphosphatidylcholine and said ratio is about 1:25 to about 1:40.  
     
     
         13 . A liposome produced by the following steps: 
 dissolving a lipid-soluble anticancer drug in an appropriate solvent to produce dissolved anticancer drug;    dissolving a lipid suitable for the formulation and delivery of anticancer drugs by aerosol in an appropriate solvent to produce dissolved lipid;    combining said dissolved anticancer drug and said dissolved lipid to produce a solution, wherein said dissolved anticancer drug is at a concentration not exceeding about 10% of the total volume of said solution and a ratio of said anticancer drug to said suitable lipid is in a range of 1:1 to 1:200 wt:wt of said solution; and    evaporating said solvents from said solution to produce a powder.    
     
     
         14 . The liposome of  claim 13 , further comprising the step of dissolving said powder in sterile water to produce a suspension, wherein a concentration of said anticancer drug in said sterile water is no more than about 5.0 mg/ml.  
     
     
         15 . The liposome of  claim 13  wherein said suitable lipid for formulating and delivering drugs by aerosol is dilauroylphosphatidylcholine.  
     
     
         16 . The liposome of  claim 13 , wherein said anti-cancer drug is selected from the group consisting of 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, 10,11-methylenedioxy-camptothecin, taxol, taxol-A, mitotane, methotrexate, mercaptopurine, lomustine, interferon, 5-fluorouracil and etopiside.  
     
     
         17 . The liposome of  claim 13 , wherein said anti-cancer drug is selected from the group consisting of 20-S-Camptothecin, 9-Nitro-camptothecin, 9-Amino-camptothecin and 10,11-methylenedioxy-camptothecin, and taxol.  
     
     
         18 . The liposome of  claim 13 , wherein a ratio of anticancer drug to lipid is about 1:10 to about 1:100 wt:wt.  
     
     
         19 . The liposome of  claim 18 , wherein a ratio of anticancer drug to lipid is about 1:10 to about 1:50 wt:wt.  
     
     
         20 . A liposome produced by the following steps: 
 dissolving a lipid-soluble anticancer drug selected from the group of 20-S-camptothecin (CPT), 9-nitrocamptothecin (9-NC) and other lipid soluble camptothecin derivatives in a volume of DMSO to produce dissolved anticancer drug;    mixing said dissolved anticancer drug with an appropriate solvent;    dissolving a lipid suitable for the formulation and delivery of drugs by aerosol in an appropriate solvent to produce a dissolved lipid;    combining said dissolved anticancer drug and said dissolved lipid to produce a solution, wherein said DMSO is at a concentration not exceeding about 10% of the total volume of said solution and a ratio of said anticancer drug to said suitable lipid is in a range of 1:1 to 1:200 of said solution; and    evaporating said solvents from said solution to produce a powder.    
     
     
         21 . The liposome of claim  20 , wherein said lipid is dilauroylphosphatidylcholine.