Multifunctional and biologically active matrices from multicomponent polymeric solutions

• US 7,732,427 B2
• Filed: 03/31/2006
• Issued: 06/08/2010
• 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, Rabolt, John, Casper, Cheryl
• Primary Examiner(s): Jiang; Shaojia Anna
• Assistant Examiner(s): Henry; Michael C
• Application Number:
  US11/395,699
• Publication Number:
  US 20060240110A1
• Time in Patent Office: 1,530 Days
• Field of Search: 514/56, 514/54, 514/23, 514/2, 536/21, 424/488, 424/486
• US Class Current: 514/56
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• 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

The present invention relates to a biologically active functionalized electrospun matrix to permit immobilization and long-term delivery of biologically active agents. In particular the invention relates to a functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer and a biomolecule or other small functioning molecule. In certain aspects the electrospun polymer fibers comprise at least one biologically active molecule functionalized with low molecular weight heparin. Examples of active molecules that may be used with the multicomponent polymer of the invention include, for example, a drug, a biopolymer, for example a growth factor, a protein, a peptide, a nucleotide, a polysaccharide, a biological macromolecule or the like. The invention is further directed to the formation of functionalized crosslinked matrices, such as hydrogels, that include at least one functionalized compatibilizing polymer capable of assembly.

Claims

1. A functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer, wherein the compatibilizing polymer comprises PEG, and a small molecule, wherein the small molecule comprises LMWH or heparin-binding peptide and is covalently attached to the compatibilizing polymer, wherein the polymer matrix comprises between about 0.35% wt/wt and about 0.95% wt/wt compatibilizing polymer and is capable of forming a drug delivery device for the in situ delivery of therapeutic compounds.

2. The polymer matrix of claim 1 wherein the compatibilizing polymer comprises a moderate molecular weight PEG having a chemical composition that can be chemically modified with said small molecule.

3. The polymer matrix of claim 1 wherein the matrix polymer is selected from the group consisting of PEO and PLGA.

4. The polymer matrix of claim 1 wherein the small molecule comprises LMWH.

5. The polymer matrix of claim 1 further comprising a growth factor.

6. An electrospun fiber comprising the polymer matrix of claim 1.

7. The fiber of claim 6 wherein the fiber'"'"'s diameter is between about 50 and about 400 nm.

8. The fiber of claim 6 wherein the small molecule comprises LMWH.

9. The fiber of claim 6 wherein the fiber contains at least 3 ug/mg of LMWH.

10. The fiber of claim 6 wherein the compatibilizing polymer is further associated with a growth factor.

11. The polymer matrix of claim 1 wherein the compatibilizing polymer comprises four-arm star PEG.

12. The fiber of claim 10 wherein less than about 10% wt/wt of the growth factor is released within 24 hours after incubation in 1 mL of 2.5 ug/mL of phosphate buffer saline at a temperature of 4°

C.

13. A functionalized polymer matrix comprising a matrix polymer, a compatibilizing polymer and a small molecule, wherein the small molecule comprises LMWH or heparin-binding peptide and is covalently attached to the compatibilizing polymer, wherein the polymer matrix comprises between about 0.35% wt/wt and about 8.5% wt/wt compatibilizing polymer and is capable of forming a drug delivery device for the in situ delivery of therapeutic compounds, and wherein the compatibilizing polymer comprises a four-arm star PEG.