Protease triggered release of molecules from hydrogels

Patent metadata

Field	Value
Publication number	US-9694081-B2
Application number	US-201113805501-A
Country	US
Kind code	B2
Filing date	Jun 17, 2011
Priority date	Jun 21, 2010
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

The invention relates to compositions comprising (i) biocompatible hydrogel and (ii) one or more therapeutic agents contained within said hydrogel; wherein the hydrogel is cross-linked utilizing a cross-linker comprising a peptide sequence that is capable of being degraded by an enzyme; the therapeutic agent being effective as a treatment of a condition related to the presence of the enzyme.

First claim

What is claimed:

1. A process for delivery of an inhibitor of matrix metalloprotease to the extracellular matrix of targeted tissue comprising:
administering a hydrogel composition to a patient; said hydrogel composition comprising:
biocompatible hydrogel, said hydrogel comprising a plurality of cross-linkers connecting backbone components of said hydrogel; and
a therapeutic agent comprising an inhibitor of matrix metalloprotease encapsulated within said hydrogel;
wherein said hydrogel is cross-linked utilizing a cross-linker comprising a peptide sequence that is capable of being degraded by a matrix metalloprotease; said inhibitor being effective as a treatment of a condition related to the presence of said matrix metalloprotease;
wherein said hydrogel contains binding groups to said inhibitor of matrix metalloprotease to retain the inhibitor within the intact hydrogel;
allowing said hydrogel composition to contact matrix metalloprotease in said extracellular matrix of targeted tissue;
said contact resulting in the release of at least a portion of said inhibitor of matrix metalloprotease.

2. The process of claim 1 , wherein said tissue inhibitor of matrix metalloprotease is TIMP-3.

3. The process of claim 1 , wherein said matrix metalloprotease is MMP-13 or MMP-2.

4. The process of claim 1 , wherein the delivery is accomplished through a syringe or catheter.

5. The process of claim 1 , wherein the delivery is accomplished by intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection.

6. The process of claim 1 , wherein said hydrogel comprises hyaluronic acid.

7. The process of claim 1 , wherein the hydrogel composition is such that encapsulated inhibitors are released from the hydrogel and into the extracellular matrix of tissue in the presence of pathological levels of matrix metalloprotease.

8. The process of claim 1 , wherein said peptide comprising a sequence GCRDGPQGIWGQDRCG, GGPQGIWGQGCG, or GCGQGWIGQPGGG.

9. The process of claim 1 , wherein said peptide sequence is incorporated into the cross-linker via reaction of thiol groups of cysteins with acrylates or methacrylates.

10. The process of claim 1 , wherein the patient is a mammal.

11. The process of claim 1 , wherein the patient is a human.

12. The process of claim 1 , wherein the delivery is accomplished through a syringe.

13. The process of claim 1 , wherein the delivery is accomplished through a catheter.

14. The process of claim 1 , wherein the patient is in need of treatment for myocardial infarction.

15. The process of claim 1 , wherein inhibitor of matrix metalloprotease reduces left ventricular remodeling associated with myocardial infarction in said patient.

16. The process of claim 1 , wherein said binding groups attenuate diffusion of encapsulated inhibitors from the hydrogel.

17. The process of claim 1 , wherein said peptide crosslinker is degraded by a matrix metalloproteinase.

18. The process of claim 1 , wherein said inhibitor diffuses from the hydrogel as the crosslinkers are degraded.

19. A process for delivery of an inhibitor of matrix metalloprotease to the extracellular matrix of targeted tissue comprising:
administering a hydrogel composition to a patient; said hydrogel composition comprising:
biocompatible hydrogel comprising hyaluronic acid, said hydrogel comprising a plurality of cross-linkers connecting backbone components of said hydrogel; and
a therapeutic agent comprising an inhibitor of matrix metalloprotease encapsulated within said hydrogel;
wherein said hydrogel is cross-linked utilizing a cross-linker comprising a peptide sequence that is capable of being degraded by a matrix metalloprotease; said inhibitor being effective as a treatment of a condition related to the presence of said matrix metalloprotease; wherein said hydrogel contains binding groups to said inhibitor of matrix metalloprotease to retain the inhibitor within the intact hydrogel;
allowing said hydrogel composition to contact matrix metalloprotease in said extracellular matrix of targeted tissue;
said contact resulting in the release of at least a portion of said inhibitor of matrix metalloprotease.

Assignees

• Burdick Jason Alan
• Gorman Robert C
• Gorman Iii Joseph H
• Purcell Brendan Patrick
• Univ Pennsylvania

Inventors

• Burdick Jason Alan
• Gorman Robert C
• Gorman Iii Joseph H
• Purcell Brendan Patrick

Classifications

• A61K47/42 Primary

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• A61K38/10

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K38/57

  from animals; from humans {(A61K38/553, A61K38/556 take precedence)} · CPC title

• A61K38/1866

  Vascular endothelial growth factor [VEGF] · CPC title

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title