Lipid-polymer conjugates, their preparation and uses thereof

Abstract

This invention provides low molecular weight lipid-GAG and phospholipids-GAG conjugates and methods of use thereof in suppressing, inhibiting, preventing, or treating a pathogenic effect on a cell, including, inter alia, infection with intracellular pathogens.

1 . A lipid-polymer conjugate comprising a glycosaminoglycan (GAG) conjugated to a phospholipid (PL) wherein said conjugate is prepared by reacting said GAG with said PL in a mass PL  to mass GAG  ratio from about 0.25:15 to about 5:15, respectively. 
     
     
         2 . The lipid-polymer conjugate of claim  0 , wherein said mass PL  to mass GAG  ratio is about 0.25:15. 
     
     
         3 . The lipid-polymer conjugate of claim  0 , wherein said mass PL  to mass GAG  ratio is about 0.5:15. 
     
     
         4 . The lipid-polymer conjugate of claim  0 , wherein said mass PL  to mass GAG  ratio is about 1:15. 
     
     
         5 . The lipid-polymer conjugate of claim  0 , wherein said mass PL  to mass GAG  ratio is about 2:15. 
     
     
         6 . The lipid-polymer conjugate of claim  0 , wherein said mass PL  to mass GAG  ratio is about 5:15. 
     
     
         7 . The lipid-polymer conjugate of claim  0 , wherein said GAG is hyaluronic acid, heparin, heparan sulfate, chondroitin, chondroitin sulfate, dermatan sulfate or keratan sulfate. 
     
     
         8 . The lipid-polymer conjugate of claim  0 , wherein said PL is a phosphatidylethanolamine, a phosphatidylserine, a phosphatidylcholine, a phosphatidylinositol, a phosphatidic acid or a phosphatidylglycerol. 
     
     
         9 . The lipid-polymer conjugate of claim  0 , wherein said PL comprises the residue of palmitic acid or myristic acid. 
     
     
         10 . The lipid-polymer conjugate of claim  0 , wherein said PL is dimyristoyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine. 
     
     
         11 . The lipid-polymer conjugate of claim  0 , wherein the polydispersity of said GAG is from about 1 to 1.75. 
     
     
         12 . The lipid-polymer conjugate of  claim 11 , wherein the polydispersity of said GAG is from about 1.25 to 1.5. 
     
     
         13 . The lipid-polymer conjugate of claim  0 , wherein the average molecular weight of said GAG is between 5 KD to 90 KD. 
     
     
         14 . The lipid-polymerconjugate of  claim 13 , wherein the average molecular weight of said GAG is between 5 KD to 20 KD. 
     
     
         15 - 23 . (canceled) 
     
     
         24 . A lipid-polymer conjugate comprising a glycosaminglycan (GAG) conjugated to a phospholipid (PL) via an amide or ester linkage wherein the molecular weight of said GAG is between 5 to 20 KD and wherein the polydispersity of said GAG is from about 1 to 1.75. 
     
     
         25 . The lipid-polymer conjugate of  claim 24 , wherein the polydispersity of said GAG is from about 1.25 to 1.5. 
     
     
         26 . The lipid-polymer conjugate of  claim 24 , wherein said GAG is hyaluronic acid, heparin, heparan sulfate, chondroitin, chondroitin sulfate, dermatan sulfate or keratan sulfate. 
     
     
         27 . The lipid-polymer conjugate of  claim 24 , wherein said PL is a phosphatidylethanolamine, a phosphatidylserine, a phosphatidylcholine, a phosphatidylinositol, a phosphatidic acid or a phosphatidylglycerol. 
     
     
         28 . The lipid-polymer conjugate of  claim 24 , wherein said PL comprises the residue of palmitic acid or myristic acid. 
     
     
         29 . The lipid-polymer conjugate of  claim 24 , wherein said PL is dimyristoyl phosphatidylethanolamine or dipalmitoyl phosphatidylethanolamine. 
     
     
         30 . A pharmaceutical composition comprising the lipid-polymer conjugate of  claim 1 . 
     
     
         31 . A pharmaceutical composition comprising the lipid-polymer conjugate of  claim 24 .