Enhanced circulation effector composition and method

Abstract

A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

1 . A liposome composition, comprising 
 liposomes, each having an outer layer of a hydrophilic, and    an effector molecule attached to the distal ends of said chains, said effector molecule having binding affinity to a cell receptor,    wherein said liposome-bound effector molecule binds to the cell receptor and sterically hinders the cell receptor.    
     
     
         2 . The composition of  claim 1  wherein the effector molecule is selected from the group consisting of F ab  antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and  limulus  antilipopolysaccharide factor (LALF).  
     
     
         3 . The composition of  claim 2  wherein the polysaccharide is sialyl Lewis x .  
     
     
         4 . The composition of  claim 2  wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β, lymphotoxin, GM-CSF, and G-CSF.  
     
     
         5 . The composition of  claim 4  wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.  
     
     
         6 . The composition of  claim 4  wherein the interleukin is selected from the group consisting of IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.  
     
     
         7 . A liposome composition for use in treating a condition mediated by binding of one binding member to a second binding member, comprising 
 liposomes, each having an outer layer of a hydrophilic polymer,    an effector molecule attached to the distal ends of said chains, said effector molecule having binding affinity to a cell receptor,    wherein said liposome-bound effector molecule binds to the cell receptor and sterically hinders the cell receptor.    
     
     
         8 . The composition of  claim 7  wherein the effector molecule is selected from the group consisting of F ab  antibody fragments, cytokines, cellular growth factors, peptide hormones, monosaccharides, polysaccharides, IL-1 inhibitors, ELAM-1 binding inhibitors, and limulus antilipopolysaccharide factor (LALF).  
     
     
         9 . The composition of  claim 8  wherein the polysaccharide is sialyl Lewis x .  
     
     
         10 . The composition of  claim 8  wherein the cytokine is selected from the group consisting of interferons, interleukins, TNF, transforming growth factor β, lymphotoxin, GM-CSF, and G-CSF.  
     
     
         11 . The composition of  claim 10  wherein the interferon is selected from the group consisting of IFN-alpha, IFN-beta, and IFN-gamma.  
     
     
         12 . The composition of  claim 10  wherein the interleukin is selected from the group consisting of IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, and IL-8.