Multifunctional polymeric tissue coatings

• US 7,316,845 B2
• Filed: 03/19/2004
• Issued: 01/08/2008
• Est. Priority Date: 04/21/1997
• Status: Expired due to Fees

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Hubbell, Jeffrey A., Elbert, Donald L., Herbert, Curtis B.
• Primary Examiner(s): Jackson; Monique R.
• Application Number:
  US10/804,787
• Publication Number:
  US 20060122290A1
• Time in Patent Office: 1,390 Days
• Field of Search: 428/426, 428/457
• US Class Current: 428/426
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C08G 81/00 Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers involving only carbon-to-carbon unsaturated bond reactions C08F299/00 ; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42
• CPC Class Codes: Y10T 428/31504 Composite [nonstructural laminate]
• CPC Class Codes: Y10T 428/31678 Of metal
• CPC Class Codes: Y10T 428/31725 Of polyamide
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31971 Of carbohydrate

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.

Claims

1. A medical device or implant formed of a material with a net anionic surface, wherein the material is selected from the group consisting of metal or glass having a surface coating adsorbed thereto comprising

a block copolymer in a form selected from the group consisting of brush copolymers, dendritic copolymers and linear copolymers,

wherein the copolymer comprises a polycationic block comprising either a linear polycationic block or a dendritic polycationic block with a molecular weight sufficient to provide at least eight cationic charges, and at least one non-tissue binding block,

wherein when the copolymer is in the form of a brush copolymer, the polycationic block is not polyethylene imine,

wherein the block copolymer is applied to the surface to form a coating by ionic binding of the cationic charges to the surface, and

wherein the non-tissue binding block prevents or minimizes the attachment of proteins or cells to the surface.

2. The implant or device of claim 1, wherein the surface is a glass surface.

3. The implant or device of claim 1, wherein the surface is a metal surface.

4. The implant or device of claim 1, wherein the surface is net anionic at physiological pH.

5. The device or implant of claim 1, wherein the non-tissue-binding block has a molecular weight in excess of 5,000 daltons.

6. The device or implant of claim 1, where the non-tissue-binding block has a molecular weight in excess of 50,000 daltons.

7. The device or implant of claim 1, wherein the non-tissue-binding 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.

8. The device or implant of claim 7, wherein the non-tissue-binding block comprises polyethylene glycol.

9. The device or implant of claim 1, wherein the polycationic block 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.

10. The device or implant of claim 9, wherein the positively charged polysaccharide is selected from the group consisting of chitosan, partially deacetylated chitin, and amine-containing derivatives of neutral polysaccharides.

11. The device or implant of claim 9 wherein the positively charged synthetic polymer is selected from the group consisting of polyethyleneimine, polyamino(meth)acrylate, polyaminostyrene, polyaminoethylene, poly(aminoethyl)ethylene, polyaminoethylstyrene, and N-alkyl derivatives thereof.

12. The device or implant of claim 1, wherein the polycationic block comprises monomeric units selected from the group consisting of lysine, histidine, arginine and ornithine.

13. The device or implant of claim 1, further comprising a bioactive agent.

14. The device or implant of claim 13 wherein the bioactive agent is chemically coupled to the polymer.

15. A method for coating the surface of a medical device or implant formed of a material with a net anionic surface, selected from the group consisting of metal and glass, comprising adsorbing to the surface a block copolymer,

wherein the copolymer is in a form selected from the group consisting of brush copolymers, dendritic copolymers and linear copolymers,

wherein the copolymer comprises a polycationic block comprising either a linear polycationic block or a dendritic polycationic block with a molecular weight sufficient to provide at least 8 cationic charges and at least one non-tissue binding block,

wherein when the copolymer is in the form of a brush copolymer, the polycationic block is not polyethylene imine,

wherein the block copolymer is applied to the surface to form a coating by ionic binding of the cationic charges to the surface, and

wherein the non-tissue binding block prevents or minimizes the attachment of proteins or cells to the surface.

16. The method of claim 15, wherein the surface is a metal surface.

17. The method of claim 15, wherein the surface is a glass surface.

18. The method of claim 15, wherein the surface is net anionic at physiological pH.

19. The method of claim 15, wherein the copolymer is applied to the surface by placing the medical device or implant in a solution containing the copolymer.