Large liposome composition not increasing ldl levels and method of treating atherosclerosis related thereto

Abstract

The present invention provides a pharmaceutical composition consisting essentially of large liposomes comprised of phospholipids substantially free of sterol. The composition forces the reverse transport of cholesterol from peripheral tissues to the liver in vivo. The invention further provides a method of treating atherosclerosis in a subject comprising the step of administering a liposome composition to the subject. The liposome composition is selected from the group consisting of unilamellar liposomes and multilamellar liposomes and the liposomes have an average diameter of about 50-150 nanometers. LDL levels in said subject do not increase with utilization of the method. The invention also provides a method of controlling cholesterol metabolism in hepatic parenchymal cells in a subject in vivo through cell-cell communication from Kupffer cells to the parenchymal cells. The method includes the step of administering a liposome composition to a subject. The liposome composition is selected from the group consisting of large unilamellar liposomes and large multilamellar liposomes, and the liposomes having an average diameter of about 50-150 nanometers. Similarly, LDL levels in the subject do not increase. In variants, the liposome composition is given periodically, given more than once, or given in repeated doses. The liposomes have diameters larger than about 50 nm, diameters larger than about 80 nm, and diameters larger than about 100 nm in different variants. The liposomes are phospholipids selected from the group consisting of phosphatidyl choline, phosphatidyl glycerol, palmitoyl-oleoyl phosphatidyl choline, combinations thereof, and derivatives thereof.

I claim:  
     
         1 . A pharmaceutical composition consisting essentially of: 
 large liposomes comprised of phospholipids substantially free of sterol, whereby said composition forces the reverse transport of cholesterol from peripheral tissues to the liver in vivo.    
     
     
         2 . A method of treating atherosclerosis in a subject comprising the step of administering a liposome composition to said subject, said liposome composition selected from the group consisting of unilamellar liposomes and multilamellar liposomes, said liposomes having an average diameter of about 50-150 nanometers, in which LDL levels in said subject do not increase.  
     
     
         3 . A method of controlling cholesterol metabolism in hepatic parenchymal cells in a subject in vivo through cell-cell communication from Kupffer cells to said parenchymal cells, comprising the step of administering a liposome composition to said subject, said liposome composition selected from the group consisting of large unilamellar liposomes and large multilamellar liposomes, said liposomes having an average diameter of about 50-150 nanometers, in which LDL levels in said subject do not increase.  
     
     
         4 . The method in accordance with  claim 3  in which the liposome composition is given periodically.  
     
     
         5 . The method in accordance with  claim 3  in which the liposome composition is given more than once.  
     
     
         6 . The method in accordance with  claim 3  in which the liposomes have diameters larger than about 50 nm.  
     
     
         7 . The method in accordance with  claim 3  in which the liposomes have diameters larger than about 80 nm.  
     
     
         8 . The method in accordance with  claim 3  in which the liposomes have diameters larger than about  100  nm.  
     
     
         9 . The method in accordance with  claim 3  in which administration is selected from the group of parenteral administration, intravenous administration, intra-arterial administration, intramuscular administration, subcutaneous administration, transdermal administration, intraperitoneal administration, intrathecal administration, via lymphatics, intravascular administration, including administration into capillaries and arteriovenous shunts, rectal administration, administration via a chronically indwelling catheter, and administration via an acutely placed catheter.  
     
     
         10 . The method in accordance with  claim 3  in which about 10 to about 1600 mg/kg/dose of said liposome composition is administered.  
     
     
         11 . The method in accordance with  claim 3  in which the liposome composition is given in repeated doses.  
     
     
         12 . The method in accordance with  claim 3  in which the liposomes are phospholipids substantially free of sterol and in the range of about 50-150 nm in approximate diameter.  
     
     
         13 . The method in accordance with  claim 3  in which the liposomes are phospholipids substantially free of sterol.  
     
     
         14 . The method in accordance with  claim 3  in which the liposomes are phospholipids selected from the group consisting of phosphatidyl choline, phosphatidyl glycerol, palmitoyl-oleoyl phosphatidyl choline, combinations thereof, and derivatives thereof.