Polycationic peptide coatings and methods of making the same

• US 7,011,842 B1
• Filed: 06/21/2002
• Issued: 03/14/2006
• Est. Priority Date: 06/21/2002
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pacetti, Stephen D., Ding, Ni, Simhambhatla, Murthy V
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US10/177,114
• Time in Patent Office: 1,362 Days
• Field of Search: 424/426, 424/486
• US Class Current: 424/426
• CPC Class Codes: A61L 2300/114 Nitric oxide, i.e. NO
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 77/04 Polyamides derived from alpha-amino carboxylic acids C08L77/10 takes precedence

Abstract

Polycationic peptide coatings for implantable medical devices and methods of making the same are described. The methods include applying an emulsion on the device, the emulsion including a polymer and a polycationic peptide. Other methods include incorporation of the polycationic peptide in microspheres and liposomes.

Claims

1. A method of coating an implantable medical device, comprising applying an emulsion of a polymer and a polycationic peptide on the device to form a coating for the device.

2. The method of claim 1, wherein the device is a stent.

3. The method of claim 1, wherein the polycationic peptide includes poly(L-arginine), poly(D-arginine), poly(D,L-arginine), a mixture of poly(L-arginine) and poly(D-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), or mixtures thereof.

4. The method of claim 1, wherein the polymer comprises an acrylic polymer, a vinyl polymer, a polyurethane, or a combination thereof.

5. The method of claim 4, wherein the acrylic polymer is selected from a group consisting of poly(butyl methacrylate) and poly(methyl methacrylate).

6. The method of claim 4, wherein the vinyl polymer is selected from a group consisting of poly(ethylene-co-vinyl alcohol) and poly(vinyl acetate).

7. The method of claim 1, wherein the emulsion further comprises a first surfactant.

8. The method of claim 7, wherein the first surfactant has a hydrophilic-lipophilic balance between about 3 and about 6.

9. The method of claim 8, wherein the emulsion additionally comprises a second surfactant having has a hydrophilic-lipophilic balance exceeding the value of 10.

10. The method of claim 1, wherein the emulsion is a water-in-oil emulsion.

11. A coating for an implantable medical device, the coating fabricated by the method of claim 1.

12. A method for incorporating a polycationic peptide into a coating for an implantable medical device, the method comprising:

(a) fabricating microspheres containing the polycationic peptide;

(b) dispersing the microspheres in a polymer solution; and

(c) applying the solution onto the device.

13. The method of claim 12, wherein the medical device is a stent.

14. The method of claim 12, wherein the polycationic peptide includes poly(L-arginine), poly(D-arginine), poly(D,L-arginine), a mixture of poly(L-arginine) and poly(D-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), or mixtures thereof.

15. The method of claim 12, wherein the fabrication of the microspheres includes emulsification of an aqueous solution of the polycationic peptide in an organic solvent medium.

16. The method of claim 15, wherein the organic solvent is selected from a group consisting of cyclooctane, cyclohexane, cycloheptane, para-xylene, dimethylformamide, dimethylsulfoxide, chloroform, methylene oxide, dimethylacetamide, and mixtures thereof.

17. The method of claim 12, wherein a polymer in the polymer solution is selected from the group consisting of poly(ethylene-co-vinyl alcohol), poly(vinyl acetate), poly(butyl methacrylate), poly(methyl methacrylate), poly(urethane), poly(L-lactide), poly(D,L-lactide), poly(glycolide), poly(caprolactone), polyanhydrides, polydiaxanone, polyorthoesters, polyamino acids, poly(trimethylene carbonate), and combinations thereof.

18. A coating for an implantable medical device, the coating fabricated by the method of claim 12.

19. A method for incorporating a polycationic peptide into a coating for an implantable medical device, the method comprising:

(a) fabricating liposomes containing the polycationic peptide;

(b) dispersing the liposomes in a polymer solution; and

(c) applying the solution onto the device.

20. The method of claim 19, wherein the medical device is a stent.

21. The method of claim 19, wherein the polycationic peptide includes poly(L-arginine), poly(D-arginine), poly(D,L-arginine) a mixture of poly(L-arginine) and poly(D-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), or a mixture thereof.

22. The method of claim 19, wherein the fabrication of the liposomes includes suspending a lipid in an aqueous medium solution in the presence of the polycationic peptide.

23. The method of claim 22, wherein the lipid is phosphatidylcholine.

24. The method of claim 22, further comprising isolation and purification of the liposomes.

25. The method of claim 24, wherein the isolation and purification is achieved by dialysis or gel-filtration chromatography.

26. The method of claim 19, wherein a polymer in the polymer solution is selected from the group consisting of poly(ethylene-co-vinyl alcohol), poly(vinyl acetate), poly(butyl methacrylate), poly(methyl methacrylate), and poly(urethane).

27. A coating for an implantable medical device, the coating fabricated by the method of claim 19.