CELL-MEDIATED DELIVERY AND TARGETED EROSION OF NONCOVALENTLY CROSSLINKED HYDROGELS

• US 20100317110A1
• Filed: 06/14/2010
• Published: 12/16/2010
• Est. Priority Date: 03/31/2005
• Status: Active Grant

• Current Assignee: University of Delaware
• Original Assignee: University of Delaware
• Inventors: Kiick, Kristi L., Yamaguchi, Nori
• Granted Patent: US 8,415,325 B2
• Time in Patent Office: Days
• US Class Current: 435/375
• CPC Class Codes: A61K 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092

Abstract

A method for targeted delivery of therapeutic compounds from hydrogels is presented. The method involves administering to a cell a hydrogel in which a therapeutic compound is noncovalently bound to heparin.

Claims

1. A method for targeted delivery of a therapeutic compound to a cell, the method comprising administering a hydrogel comprising a heparin-binding therapeutic compound to a cell, wherein the cell is capable of non-covalently binding the therapeutic compound;

wherein the hydrogel comprises a cross-linked matrix comprising at least two polymer-LMWH conjugates, and at least one heparin-binding compound, wherein the polymer comprises PEG, wherein each polymer-LMWH conjugate comprises at least one polymer covalently bonded to at least one LMWH molecule, wherein a fraction of the polymer-LMWH conjugates is noncovalently bound with the heparin-binding compound, and wherein the heparin-binding compound comprises the therapeutic compound.

2. The method of claim 1, wherein the therapeutic compound is a growth factor.

3. The method of claim 2, wherein the growth factor is selected from the group consisting of vascular endothelial growth factor, basic fibroblast growth factor, acidic fibroblast growth factor, heparin-binding epidermal growth factor, transforming growth factor-beta, and nerve growth factor.

4. The method of claim 1, wherein the therapeutic compound is selected from the group consisting of peptide-modified polymers, polysaccharide-modified polymers, peptides, proteins, polysaccharides, peptoids, and small molecule drugs.

5. The method of claim 1, wherein the therapeutic compound is a growth factor agonist or antagonist modified to bind heparin.

6. The method of claim 5, wherein the therapeutic compound is selected from the group consisting of F56, V1, GU40C4, K237, and QK.

7. The method of claim 1, wherein the therapeutic compound is released from the hydrogel in the presence of a cell and specifically binds to a cell surface receptor.

8. The method of claim 7, wherein release of the therapeutic compound from the hydrogel stimulates erosion of the hydrogel.

9. The method of claim 7, wherein the rate of release of the therapeutic compound is regulated by the heparin-binding affinity of the therapeutic compound.

10. The method of claim 4, wherein the peptide-modified polymer is modified with a peptide selected from the group consisting of SEQ ID NO:

4, 5, 6, and 7.

11. The method of claim 1, wherein the polymer of each polymer-LMWH conjugate is covalently crosslinked to a polymer matrix.