Self-assembling peptide amphiphiles and related methods for growth factor delivery

• US 20050209145A1
• Filed: 12/06/2004
• Published: 09/22/2005
• Est. Priority Date: 12/05/2003
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Donners, Jack J.J.M., Stupp, Samuel I., Silva, Gabriel A., Behanna, Heather A., Anthony, Shawn G.
• Granted Patent: US 7,544,661 B2
• Time in Patent Office: Days
• US Class Current: 514/8.100
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

Claims

1. An amphiphilic peptide compound comprising a peptide component and a hydrophobic component, said peptide component comprising a growth factor recognition product of a phage display process, said recognition product coupled to said peptide component at about the N-terminus thereof, said hydrophobic component coupled to said peptide component at about the C-terminus thereof.

2. The compound of claim 1 wherein said recognition product is selected from epitope sequences providing binding interactions with growth factors BMP-2, TGF-β

1, VEGF, FGF-2, NT-3 and laminin-5.

3. The compound of claim 2 wherein said binding epitope sequence comprises YPVHPST.

4. The compound of claim 3 wherein said sequence is in a non-covalent binding interaction with growth factor BMP-2.

5. The compound of claim 2 wherein said binding epitope sequence comprises LPLGNSH.

6. The compound of claim 5 wherein said sequence is in a non-covalent binding interaction with growth factor TGF-β

1.

7. The compound of claim 1 wherein said peptide component has a net charge at a physiological pH.

8. The compound of claim 7 comprising residues selected from alanine, glycine, leucine, cysteine, valine and serine.

9. The compound of claim 2 wherein said hydrophobic component comprises an alkyl moiety ranging from about C₆ to about C₂₂.

10. The compound of claim 1 wherein said peptide component is substantially linear.

11. The peptide composition comprising a plurality of a first amphiphilic peptide compound, each said compound comprising a growth factor recognition product of a phage display process coupled to a peptide component of said compound, said peptide component having a net charge at a physiological pH and coupled to a hydrophobic component at about the C-terminus thereof.

12. The composition of claim 11 further comprising a plurality of a second amphiphilic peptide compound, each said compound absent a growth factor recognition product and having a net charge at a physiological pH complementary to said net charge of said first compound.

13. The composition of claim 12 wherein the amino acid sequence of the peptide component of said second compound has a length shorter than the length of said first compound peptide amino acid sequence.

14. The composition of claim 13 comprising a micellar assembly in an aqueous medium.

15. The composition of claim 14 comprising at least one growth factor non-covalently interacting therewith.

16. The composition of claim 15 wherein said growth factor is selected from BMP-2, TGF-β

1, VEGF, FGF-2, NT-3, laminin-5 and combinations thereof.

17. The composition of claim 16 contacting a stem cell.

18. The composition of claim 11 further comprising a plurality of a second amphiphilic peptide compound, said compound comprising a peptide amino acid sequence having a length shorter than the length of said first compound peptide amino acid sequence, said second compound absent a growth factor recognition product and having a net charge at a physiological pH complementary to said net charge of said first compound.

19. The composition of claim 18 comprising a micellar assembly in an aqueous medium.

20. The composition of claim 19 contacting stem cells and comprising a growth factor non-covalently interacting with said composition.

21. A method of using an amphiphilic peptide compound to affect bioavailability of a growth factor, said method comprising:

providing a micellar assembly comprising a plurality of a first amphiphilic compound, each said compound comprising a growth factor recognition product of a phage display process coupled to a peptide component of said first compound, said peptide component having a net charge at a physiological pH and coupled to a hydrophobic component at about the C-terminus thereof, and a plurality of a second amphiphilic peptide compound comprising a peptide amino acid sequence having a length shorter than the length of first compound peptide sequence, said second compound absent a growth factor recognition product and having a net charge at a physiological pH complementary to the net charge of said first compound; and

contacting a stem cell with said assembly.

22. The method of claim 21 wherein said growth factor is produced by said stem cell.

23. The method of claim 21 wherein said growth factor is selected from BMP-2, TGF-β

1, VEGF, FGF-2, NT-3, laminin-5 and combinations thereof.

24. The method of claim 23 wherein said recognition product is selected from epitope sequences providing non-covalent interaction with one of growth factors BMP-2 and TGF-β

1.

25. The method of claim 24 wherein said epitope sequence comprises YPVHPST non-covalently interacting with growth factor BMP-2.

26. The method of claim 24 wherein said epitope sequence comprises LPLGNSH non-covalently interacting with growth factor TGF-β

1.

27. The method of claim 21 wherein said contact is sufficient for stem cell differentiation.

28. The method of claim 27 wherein said assembly comprises growth factor BMP-2 and said recognition product comprises an epitope sequence non-covalently interacting with said growth factor.

29. The method of claim 28 wherein said stem cell is a mesenchymal stem cell.

30. The method of claim 29 wherein said stem cell differentiates into bone cells.