Nanocarrier therapy for treating invasive tumors

Abstract

Liposomes of a size of less than 200 nanometers target tumors and preferentially deliver imipramine blue to tumors, including brain tumors such as gliomas. The imipramine blue decreases the invasiveness of the tumors, and inhibits tumor metastasis. The liposomes include cholesterol and chemically pure phospholipids that are essentially neutral and contain saturated fatty acids of between 16 and 18 carbon atoms, such as distearoylphosphatidyl choline, and can also include one or more pegylated phospholipids, such as DSPE-PEG.

1 . A composition for treating tumors in a patient, comprising unilamellar liposomes, of a size of less then 200 nanometers as assessed by dynamic light scattering and containing a therapeutic amount of imipramine blue, or a pharmaceutically-acceptable salt thereof, in a pharmaceutically-acceptable carrier for intravenous administration.
 wherein the liposomes comprise cholesterol and chemically pure phospholipids that are essentially neutral and contain saturated fatty acids of between 16 and 18 carbon atoms.   
     
     
         2 . The composition of  claim 1 , where in the liposomes have a size of from about 50 to about 160 nanometers. 
     
     
         3 . The composition of  claim 1 , wherein the phospholipids are synthetic phospholipids. 
     
     
         4 . The composition of  claim 1 , wherein the phospholipids comprise distearoylphosphatidyl choline. 
     
     
         5 . The composition of  claim 1 , wherein the phospholipids comprise a pegylated phospholipid. 
     
     
         6 . The composition of  claim 1 , wherein the phospholipids comprise DSPC, DSPE-PEG, and cholesterol. 
     
     
         7 . The composition of  claim 6 , wherein the ratio of DSPC/DSPE-PEG/cholesterol is about 85%/about 5%/about 10%. 
     
     
         8 . The composition of  claims 1 - 6 , further comprising an anti-tumor agent other than imipramine blue. 
     
     
         9 . A method for treating tumors in a patient, comprising introducing into the patient's bloodstream an amount of unilamellar liposomes, of a size of less than 200 nanometers and containing a therapeutic amount of imipramine blue, or a pharmaceutically-acceptable salt thereof, that preferentially delivers a quantity of the imipramine blue, or a pharmaceutically-acceptable salt therof, to the tumor,
 wherein the liposomes comprise cholesterol and chemically pure phospholipids that are essentially neutral and contain saturated fatty acids of between 16 and 18 carbon atoms.   
     
     
         10 . The method of  claim 9 , wherein the liposomes have a size of from about 50 to about 160 nanometers. 
     
     
         11 . The method of  claim 9 , wherein the phospholipids are synthetic phospholipids. 
     
     
         12 . The method of  claim 9 , wherein the phospholipids comprise distearoylphosphatidyl choline. 
     
     
         13 . The method of  claim 9 , wherein the phospholipids comprise a pegylated phospholipid. 
     
     
         14 . The method of  claim 9 , wherein the tumor is a brain tumor. 
     
     
         15 . The method of  claim 8 , wherein the tumor is a glioma. 
     
     
         16 . The method of  claim 9 , wherein the imipramine bine inhibits tumor invasiveness. 
     
     
         17 . The method of  claim 9 , wherein the imipramine blue inhibits tumor metastasis. 
     
     
         18 . The method of  claim 9 , wherein the imipramine blue is administered in combination with another anti-cancer agent. 
     
     
         19 . Use of a composition comprising unilamellar liposomes with a size of less than 200 nanometers and containing a therapeutic amount of imipramine blue, or a pharmaceutically-acceptable salt thereof, which liposomes preferentially deliver a quantity of the imipramine blue, or a pharmaceutically-acceptable salt thereof to a tumor following administration, in the preparation of a medicament for treating tumors,
 wherein the liposomes comprise cholesterol and chemically pure phospholipids that are essentially neutral and contain saturated fatty acids of between 16 and 18 carbon atoms.   
     
     
         20 . The use of  claim 19 , wherein the liposomes have a size of from about 50 to about 160 nanometers. 
     
     
         21 . The use of  claim 19 , wherein the phospholipids are synthetic phospholipids. 
     
     
         22 . The use of  claim 19 , wherein the phospholipids comprise distearoylphosphatidyl choline. 
     
     
         23 . The use of  claim 19 , wherein the phospholipids comprise a pegylated phospholipid. 
     
     
         24 . The use of  claim 19 , wherein the tumor is a brain tumor. 
     
     
         25 . The use of  claim 19 , wherein the tumor is a glioma. 
     
     
         26 . The use of  claim 19 , wherein the imipramine blue inhibits tumor invasiveness. 
     
     
         27 . The use of  claim 19 , wherein the imipramine blue inhibits tumor metastasis. 
     
     
         28 . A composition of any of  claims 1 - 8  for use in treating tumors.