Multifunctional polymeric tissue coatings

Abstract

Compositions for coating biological and non-biological surfaces, which minimize or prevent cell-cell contact and tissue adhesion, and methods of preparation and use thereof are disclosed. Embodiments include polyethylene glycol/polylysine (PEG/PLL) block or comb-type copolymers with high molecular weight PLL (greater than 1000, more preferably greater than 100,000); PEG/PLL copolymers in which the PLL is a dendrimer which is attached to one end of the PEG; and multilayer compositions including alternating layers of polycationic and polyanionic materials. The multi-layer polymeric material is formed by the ionic interactions of a polycation and a polyanion. The molecular weights of the individual materials are selected such that the PEG portion of the copolymer inhibits cellular interactions, and the PLL portion adheres well to tissues. The compositions and methods are useful, for example, in inhibiting formation of post-surgical adhesions, protecting damaged blood vessels from thrombosis and restenosis, and decreasing the extent of metastasis of attachment-dependent tumor cells. The compositions and methods are also useful for coating non-biological surfaces such as metallic surfaces.

1 - 3 . (canceled) 
     
     
         4 . The composition of  claim 48 , wherein the non-ionic polymer is selected from the group consisting of polyethylene glycol, mixed polyalkylene oxides having a solubility of at least one gram/liter in aqueous solutions, neutral water-soluble polysaccharides, polyvinyl alcohol, poly-N-vinyl pyrrolidone, non-cationic poly(meth)acrylates and combinations thereof. 
     
     
         5 . The composition of  claim 4 , wherein the non-ionic polymer is polyethylene glycol (PEG). 
     
     
         6 . The composition of  claim 48 , wherein the polycationic dendrimer is selected from the group consisting of natural and unnatural polyamino acids having net positive charge at neutral pH, positively charged polysaccharides, and positively charged synthetic polymers. 
     
     
         7 . The composition of  claim 48 , wherein the polycationic dendrimer comprises monomeric units selected from the group consisting of lysine, histidine, arginine and ornithine. 
     
     
         8 - 10 . (canceled) 
     
     
         11 . The composition of  claim 48 , further comprising a bioactive agent. 
     
     
         12 - 40 . (canceled) 
     
     
         41 . A method for coating a non-biological surface comprising applying to the surface a two-domain block copolymer
 wherein the first domain comprises a non-ionic block, and wherein the second domain comprises a polycationic block,   wherein the surface has a net anionic charge at physiologic pH, and   wherein the polycationic block forms ionic bonds with the surface.   
     
     
         42 . The method of  claim 41 , wherein the surface is a metal surface. 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 41 , wherein the surface is the surface of a medical device. 
     
     
         45 - 47 . (canceled) 
     
     
         48 . A composition comprising a dendritic copolymer, comprising
 a polycationic dendrimer with a molecular weight sufficient to provide at least 8 cationic charges,   and a non-ionic polymer covalently linked to the dendrimer,   wherein the composition is in a form suitable for application to a biological or non-biological surface.   
     
     
         49 . The composition of  claim 11 , wherein the bioactive agent is covalently attached to the dendritic copolymer. 
     
     
         50 . The composition of  claim 11 , wherein the bioactive agent is linked to the copolymer via a biodegradable linkage. 
     
     
         51 . The composition of  claim 50 , wherein the biodegradable linkage is selected from the group consisting of anhydride, ester, amide, and carbonate linkages. 
     
     
         52 . The composition of  claim 11 , wherein the bioactive agent is selected from the group consisting of proteins, polysaccharides, organic compounds with drug activity, and nucleic acids. 
     
     
         53 . The composition of  claim 5 , wherein the cationic dendrimer comprises poly-L-lysine (PLL). 
     
     
         54 . A coating on a non-biological surface, comprising a two-domain block copolymer,
 wherein the first domain comprises a non-ionic block, and   wherein the second domain comprises a polycationic block,   wherein the surface has a net anionic charge at physiologic pH, and   wherein the polycationic block forms ionic bonds with the surface.   
     
     
         55 . The coating of  claim 54 , wherein the non-ionic block is selected from the group consisting of polyethylene glycol, mixed polyalkylene oxides having a solubility of at least one gram/liter in aqueous solutions, neutral water-soluble polysaccharides, polyvinyl alcohol, poly-N-vinyl pyrrolidone, non-cationic poly(meth)acrylates and combinations thereof. 
     
     
         56 . The coating of  claim 55 , wherein the non-ionic block comprises polyethylene glycol (PEG). 
     
     
         57 . The coating of  claim 54 , wherein the polycationic block comprises a polymer selected from the group consisting of natural and unnatural polyamino acids having net positive charge at neutral pH, positively charged polysaccharides, and positively charged synthetic polymers. 
     
     
         58 . The coating of  claim 54 , wherein the polycationic block comprises monomeric units selected from the group consisting of lysine, histidine, arginine and ornithine. 
     
     
         59 . The coating of  claim 54 , further comprising a bioactive agent. 
     
     
         60 . The coating of  claim 56 , wherein the polycationic block comprises poly-L-lysine (PLL). 
     
     
         61 . The coating of  claim 54 , wherein the surface is selected from the group consisting of hollow fibers, spiral modules, and flat sheets. 
     
     
         62 . The coating of  claim 54 , wherein the non-biological surface is the surface of a medical device or implant. 
     
     
         63 . The coating of  claim 54 , wherein the surface is formed of a material selected from the group consisting of metal, glass, ceramic, and polymer.