US2008248095A1PendingUtilityA1

Small particle liposome aerosols for delivery of anti-cancer drugs

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Individually held — no corporate assignee on recordPriority: Sep 23, 1997Filed: Jan 25, 2008Published: Oct 9, 2008
Est. expirySep 23, 2017(expired)· nominal 20-yr term from priority
Inventors:Beppino C. GiovanellaJ. Vernon KnightJ. Clifford WaldrepNedezhda KoshkinaBrian GilbertClyde W. Wellen
A61P 31/00A61P 35/00A61K 31/7048A61K 9/127A61K 31/03A61K 31/519A61K 38/21A61K 31/337A61K 31/513A61K 9/0078A61K 31/175A61K 31/4745A61K 31/52
62
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Claims

Abstract

The small particle liposome aerosol compounds and methods of treatment of the present invention involve lipid- or water soluble anti-cancer drugs incorporated into liposomes. The liposomes 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.

Claims

exact text as granted — not AI-modified
1 - 5 . (canceled) 
     
     
         6 . A method for treating cancer, comprising the step of delivering, via small particle aerosol, an aqueous suspension of an anticancer drug in liposomes or lipid complexes to the respiratory tract of an individual in need of such treatment, wherein a final concentration of said anticancer drug in said suspension is not greater than 5.0 mg/ml. 
     
     
         7 . The method of  claim 6 , wherein the anticancer drug is a lipid-soluble anticancer drug. 
     
     
         8 . The method of  claim 6 , wherein the anticancer drug is a water-soluble anticancer drug. 
     
     
         9 . The method of  claim 6 , wherein said anti-cancer drug is selected from the group consisting of 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, 10, and 11-methylenedioxy-camptothecin. 
     
     
         10 . The method of  claim 6 , wherein the anti-cancer drug is a derivative of 20-S-camptothecin. 
     
     
         11 . The method of  claim 6 , wherein said delivering step is performed by a jet nebulizer. 
     
     
         12 . The method of  claim 6 , wherein said liposomes are sheared to a diameter of less than 500 nm by said jet nebulizer. 
     
     
         13 . The method of  claim 6 , wherein a final concentration of said anticancer drug in said liposomes or lipid complexes is not greater than 1.0 mg/ml. 
     
     
         14 . The method of  claim 6 , wherein a ratio of anticancer drug to lipid is about 1:1 to about 1:200 wt:wt. 
     
     
         15 . The method of  claim 14 , wherein a ratio of anticancer drug to lipid is about 1:10 to about 1:100 wt:wt. 
     
     
         16 . The method of  claim 15 , wherein a ratio of anticancer drug to lipid is about 1:10 to about 1:50 wt:wt. 
     
     
         17 . The method of  claim 16 , wherein a ratio of anticancer drug to lipid is about 1:25 to about 1:40 wt:wt. 
     
     
         18 . The method of  claim 6 , wherein the suspension comprises one or more lipids selected from the group consisting of dilauroylphosphatidylcholine, alpha lecithin, egg yolk phosphatidylcholine, hydrogenated soybean phosphatidylcholine, dimyristophosphatidylcholine, diolyeoyl-dipalmitoyleolyphosphatidylcholine, and dipalmitoyl phosphatidylcholine. 
     
     
         19 . The method of  claim 18 , wherein the suspension comprises dilauroylphosphatidylcholine. 
     
     
         20 . A liposome or lipid complex for delivery of an anticancer drug via small particle aerosol, wherein the ratio of anticancer drug to lipid is about 1:25 to about 1:200 wt:wt. 
     
     
         21 . The liposome or lipid complex of  claim 20 , wherein the ratio of anticancer drug to lipid is about 1:25 to about 1:100. 
     
     
         22 . The liposome or lipid complex of  claim 21 , wherein the ratio of anticancer drug to lipid is about 1:25 to about 1:40. 
     
     
         23 . The liposome or lipid complex of  claim 20 , wherein the lipid is selected from the group consisting of dilauroylphosphatidylcholine, alpha lecithin, egg yolk phosphatidylcholine, hydrogenated soybean phosphatidylcholine, dimyristophosphatidylcholine, diolyeoyl-dipalmitoyleolyphosphatidylcholine, and dipalmitoyl phosphatidylcholine. 
     
     
         24 . The liposome or lipid complex of  claim 23 , wherein the lipid is dilauroylphosphatidylcholine. 
     
     
         25 . The liposome or lipid complex of  claim 20 , wherein said anticancer drug is a lipid-soluble anticancer drug. 
     
     
         26 . The liposome or lipid complex of  claim 20 , wherein said anticancer drug is a water-soluble anticancer drug. 
     
     
         27 . The liposome or lipid complex of  claim 20 , wherein said anticancer drugs is camptothecin or a derivative of a camptothecin. 
     
     
         28 . The liposome or lipid complex of  claim 27 , wherein the camptothecin is 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, 10, and 11-methylenedioxy-camptothecin. 
     
     
         29 . The liposome or lipid complex of  claim 20 , wherein the anticancer drug is mitotane, methotrexate, mercaptopurine, lomustine, interferon, 5-fluorouracil, or etopiside. 
     
     
         30 . A method of producing a liposome, comprising the steps of:
 (a) dissolving an anticancer drug in a first solvent to produce dissolved anticancer drug and dissolving a lipid suitable for the formulation and delivery of anticancer drugs by aerosol in a second solvent to produce dissolved lipid;   (b) 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;   (c) evaporating said first solvent and said second solvent from said solution to produce a powder; and   (d) dissolving said powder in an aqueous solvent to produce a suspension, wherein a concentration of said anticancer drug in said aqueous solvent is no more than about 5.0 mg/ml.   
     
     
         31 . The method of  claim 30 , wherein said suitable lipid is selected from the group consisting of dilauroylphosphatidylcholine, alpha lecithin, egg yolk phosphatidylcholine, hydrogenated soybean phosphatidylcholine, dimyristophosphatidylcholine, diolyeoyl-dipalmitoyleolyphosphatidylcholine, and dipalmitoyl phosphatidylcholine. 
     
     
         32 . The method of  claim 30 , wherein the suspension comprises dilauroylphosphatidylcholine. 
     
     
         33 . The method of  claim 30 , wherein said anti-cancer drug is a lipid-soluble anticancer drug. 
     
     
         34 . The method of  claim 30 , wherein said anticancer drug is a water-soluble anticancer drug. 
     
     
         35 . The method of  claim 30 , wherein said anticancer drug is selected from the group consisting of 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, 10, 11-methylenedioxycamptothecin, taxol, taxol-A, mitotane, methotrexate, mercaptopurine, lomustine, interferon, 5-fluorouracil and etopiside. 
     
     
         36 . The method of  claim 30 , wherein a ratio of anticancer drug to lipid is about 1:10 to about 1:100 wt:wt. 
     
     
         37 . The method of  claim 36 , wherein a ratio of anticancer drug to lipid is about 1:10 to about 1:50 wt:wt. 
     
     
         38 . The method of  claim 37 , wherein a ratio of anticancer drug to lipid is about 1:25 to about 1:40 wt:wt. 
     
     
         39 . The method of  claim 30 , wherein the first solvent and the second solvent are each independently selected from the group consisting of butanol, tert-butanol, DMSO, saline, and sterile water. 
     
     
         40 . The method of  claim 30 , wherein the aqueous solvent is sterile water.

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