Method of surface coating devices to incorporate bioactive molecules

• US 20100233225A1
• Filed: 02/11/2008
• Published: 09/16/2010
• Est. Priority Date: 02/09/2007
• Status: Abandoned Application

• Current Assignee: Bingyun Li
• Original Assignee: Bingyun Li
• Inventors: Li, Bingyun
• Application Number:
  US12/069,526
• Publication Number:
  US 20100233225A1
• Time in Patent Office: Days
• US Class Current: 424/422
• CPC Class Codes: A61K 38/208 IL-12
• 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 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A first embodiment is a coating for a surface comprising an electrostatic self-assembly creating one or more coating layer(s); (i) wherein one or more high molecular weight bioactive molecule(s) is bound to a protein carrier wherein said protein carrier or said bound bioactive molecule is further bound to one or more of said coating layer(s) and/or (ii) wherein one or more low molecular weight bioactive molecule(s) is/are incorporated within one or more of said layers or later introduced to said layer or layers by post-treatment. A second embodiment is a method of coating a surface comprising introducing said surface into a solution of one or more positively charged water-soluble polyelectrolytes at a pH ranging from about 2 to about 12 and at a temperature ranging from about 4° C. to about 80° C. and incubating said surface for about 0.5 to about 60 minutes; Rinsing said surface with said buffer solution or water to remove weakly bound material on said surface and dry by means known to one skilled in the art; Introducing said surface into a solution of one or more negatively charged water-soluble polyelectrolytes at a pH ranging from about 2 to about 12 and at a temperature ranging from about 4° C. to about 80° C. and incubating said surface for about 0.5 to about 60 minutes; and Rinsing said surface with said buffer solution or water to remove weakly bound material on said surface and passively or actively drying said surface.

Claims

1. A coating for a surface comprising:

an electrostatic self-assembly creating one or more coating layer(s) (i) wherein one or more high molecular weight bioactive molecule(s) is bound to a protein carrier wherein said protein carrier or said bound bioactive molecule is further bound to one or more of said coating layer(s) and/or (ii) wherein one or more low molecular weight bioactive molecule(s) is/are incorporated within one or more of said layers or later introduced to said layer or layers by post-treatment.

2. The coating of claim 1 wherein said coating is for the surface of an indwelling medical device.

3. The coating of claim 1 wherein said coating is for a metal, ceramic, or polymer surface.

4. The coating of claim 1 wherein one or more of said high molecular weight bioactive molecule(s) is/are chosen from the group consisting of Interleukin-12, drugs, antibiotics, cytokines, growth factors, growth inhibitors, genetic material, cells, and binding ligands.

5. The coating of claim 1 wherein said protein carrier(s) is/are chosen from the group consisting of bovine serum albumin, sterol carrier proteins, glycolipid transfer proteins, transmembrane proteins, and acyl carrier proteins.

6. The coating of claim 1 wherein said protein carrier(s) also protects the bioactivity of said high molecular weight bioactive molecule(s) and/or protects said high molecular weight bioactive molecule(s) from denature and/or destruction.

7. The coating of claim 1 wherein one or more of said low molecular weight bioactive molecule(s) is/are chosen from the group consisting of drugs, antibiotics, cytokines, growth factors, growth inhibitors, silver, zinc oxide, antimicrobial agents, anti-coagulants, RGD-containing compounds, chemotherapeutic agents, quantum dots and binding ligands.

8. The coating of claim 1 wherein one or more of said high-molecular weight bioactive molecule(s) or low-molecular weight bioactive molecule(s) are bound to the said layer(s) through covalent bonds.

9. The coating of claim 1 wherein the sustained release of one or more of said high-molecular weight bioactive molecule(s) or low-molecular weight bioactive molecule(s) is controlled by diffusion, and environmental pH.

10. The coating of claim 1 wherein one or more of said coating layer(s) are biodegradable.

11. The coating of claim 10 wherein the rate of decay of said biodegradable layer(s) may range from about several hours to about more than one year.

12. The coating of claim 10 wherein the sustained release of one or more of said high-molecular weight bioactive molecule(s) or low-molecular weight bioactive molecule(s) is controlled by one or more of the rate of diffusion, environmental pH, and the rate of decay of said biodegradable layer(s).

13. The coating of claim 10 wherein the sequence of sustained release of two or more of said high-molecular weight bioactive molecule(s) or low-molecular weight bioactive molecule(s) is controlled by one or more of the size of the bioactive molecule(s), placement within sequential said biodegradable coating layer(s), and the interaction between the bioactive molecule(s) and the coating layer(s).

14. The coating of claim 4 wherein said high molecular weight bioactive molecules are Interleukin-12 and one or more drug molecules that can enhance wound healing wherein said high molecular weight bioactive molecules stimulate a type 1 helper T (Th1) cell response.

15. The coating of claim 1 further comprising an extracellular matrix (ECM)-like outer surface with a structure similar to the fibrillar structure of fibronectin, an extracellular matrix component, but not containing fibronectin or any extracellular matrix components.

16. The coating of claim 15 wherein said ECM-like structure is made of poly(lysine) and poly(glutamic acid).

17. A method of coating a surface comprising:

a. introducing said surface into a solution of one or more positively charged water-soluble polyelectrolytes at a pH ranging from about 2 to about 12 and at a temperature ranging from about 4°

C. to about 80°

C. and incubating said surface for about 0.5 to about 60 minutes;

b. Rinsing said surface with said buffer solution or water to remove weakly bound material on said surface and dry by means known to one skilled in the art;

c. Introducing said surface into a solution of one or more negatively charged water-soluble polyelectrolytes at a pH ranging from about 2 to about 12 and at a temperature ranging from about 4°

C. to about 80°

C. and incubating said surface for about 0.5 to about 60 minutes; and

d. Rinsing said surface with said buffer solution or water to remove weakly bound material on said surface and passively or actively drying said surface.

18. The method of claim 17 wherein one or more of said positively charged water-soluble polyelectrolyte(s) is/are chosen from the group consisting of proteins, polypeptides, polylysine, chitosan, polyethyleneimine, polyacrylamide, poly(ally amine hydrochloride), and poly(diallyldimethylammonium chloride).

19. The method of claim 17 wherein one or more of said negatively charged water-soluble polyelectrolyte(s) is/are chosen from the group consisting of proteins, polypeptides, DNA, poly(glutamic acid), albumin, interleukin-12, heparin, gelatin, alginate, dextran sulfate, hyaluronan, chondroitin, poly(acrylic acid), poly(styrenesulfonate), poly(vinylsulfonate), and nanoparticles.

20. The method of claim 17 wherein said method is repeated any number of times to obtain multilayer coatings on said surface.

21. The method of claim 17 wherein one or more bioactive molecule(s) is/are impregnated into the said surface coating by being introduced to said positively charged aqueous solution and/or said negatively charged aqueous solution.

22. The method of claim 17 wherein one or more bioactive molecule(s) is/are impregnated into said surface coating by placing said surface in solutions of said bioactive molecule(s) for about 5 seconds to about 1 week and drying.

23. The method of claim 17 wherein on or more bioactive molecule(s) is/are bound to a protein carrier wherein said protein carrier is bound to one or more of said coating layers.