Water-soluble stabilized self-assembled polyelectrolytes

Abstract

The present invention is directed toward water-soluble supramolecular self-assemblies and a process for their preparation via micellization of polyelectrolytes through the use of hydrophobic monomeric units. In this invention the polyelectrolyte segment ultimately forms the core of the supramolecular assembly whereas the shell consists of uncharged hydrophilic polymers or oligomers. It has been determined that the inclusion of the hydrophobic co-monomers to the polyelectrolyte segment forming the micelle core leads to a structure of enhanced stability.

1 . Supra molecular self-assemblies of a polyelectrolyte for use in combination with a pharmacological ingredient, comprising: 
 at least one polyelectrolyte compound selected from the group consisting of diblock copolymers, multiblock copolymers and graft copolymers,    said diblock and multiblock copolymers including at least two blocks one of which is hydrophilic and essentially uncharged, and another of which contains at least one repeating unit selected from the group consisting of anionizable or permanently-negatively charged repeating units in combination with essentially hydrophobic repeating units,    said graft copolymers comprising grafted hydrophilic and essentially non-ionic oligomers or polymers, and including anionizable units, permanently-negatively charged units or mixtures of anionizable and permanently-negatively charged units, in combinaison with essentially hydrophobic repeating units,    wherein a polyelectrolyte segment forms a core of the assembly and chemically bears non-ionic hydrophobic repeating units.    
   
   
       2 . The supramolecular self-assemblies of  claim 1 , wherein: 
 said anionizable units are repeating units that can be transformed from a non-ionic to a negatively charged state via an external stimulus.    
   
   
       3 . The supramolecular self-assemblies of  claim 2 , wherein: 
 said external stimulus is selected from the group consisting of a change in pH, ionic strength, temperature or other physico-chemical changes.    
   
   
       4 . The supramolecular self-assemblies of  claim 1 , wherein: 
 said anionizable or permanently-negatively charged block, bearing hydrophobic repeating units, is synthesized from at least one hydrophobic compound selected from the group consisting of vinyl monomers, vinyl oligomers, and vinyl polymers.    
   
   
       5 . The supramolecular self-assemblies of  claim 4 , wherein: 
 said hydrophobic compound is at least one compound selected from the group consisting of acrylate, acrylamide, alkylacrylate, alkylacrylamide, arylacrylate and arylacrylamide derivatives.    
   
   
       6 . The supramolecular self-assemblies of  claim 5 , wherein: 
 said alkyl or aryl derivatives include at least one aliphatic or aromatic moiety selected from the group consisting of acrylate, acrylamide, methacrylate and methacrylamide derivatives.    
   
   
       7 . The supramolecular self-assemblies of  claim 4 , wherein: 
 said hydrophobic compound is at least one vinyl-terminated biodegradable polyester.    
   
   
       8 . The supramolecular self-assemblies of  claim 7 , wherein: 
 said vinyl terminated biodegradable polyester is selected from the group consisting of vinyl-terminated poly(lactide) and vinyl-terminated poly ε-caprolactone).    
   
   
       9 . The supramolecular self-assemblies of  claim 1 , wherein: 
 said anionizable units include at least one functional group selected from carboxylate, phosphate and sulfate.    
   
   
       10 . The supramolecular self-assemblies of  claim 1 , wherein: 
 said hydrophilic block is synthesized from at least one hydrophilic compound selected from vinyl monomers, vinyl oligomers and vinyl polymers.    
   
   
       11 . The supramolecular self-assemblies of  claim 10 , wherein: 
 said hydrophilic compound is at least one compound selected from the group consisting of acrylate derivatives, acrylamide derivatives, alkylacrylate derivatives, alkylacrylamide, and N-vinyl-2-pyrrolidone derivatives.    
   
   
       12 . The supramolecular self-assemblies of  claim 1 , wherein: 
 said hydrophilic block originates from a macroinitiator based on poly (ethylene glycol) or poly (N-vinyl-2-pyrrolidone).    
   
   
       13 . A pharmaceutical formulation comprising supramolecular self-assemblies of  claim 1  in combination with a effective amount of at least one pharmacological constituent.  
   
   
       14 . The pharmaceutical formulation of  claim 13 , wherein the pharmacological constituent is a drug.  
   
   
       15 . The pharmaceutical formulation of  claim 13 , wherein the pharmacological constituent is a peptide, protein or genetic material.  
   
   
       16 . The pharmaceutical formulation of  claim 13 , including a targeting ligand.