Multifunctional and biologically active matrices from multicomponent polymeric solutions

• US 20060240110A1
• Filed: 03/31/2006
• Published: 10/26/2006
• Est. Priority Date: 03/31/2005
• Status: Active Grant

• Current Assignee: University of Delaware
• Original Assignee: University of Delaware
• Inventors: Yamaguchi, Nori, Kiick, Kristi L., Rabolt, John, Casper, Cheryl
• Granted Patent: US 7,732,427 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• 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 and a small functioning molecule.

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

3. The polymer matrix of claim 1 wherein the small functioning molecule comprises a biomolecule selected from the group consisting of peptides, polypeptides, sulfated peptides, sulfated polypeptides, chemically modified peptides, chemically modified polypeptides, proteins, protein fragments, growth factors, growth hormones, cytokines, insulin, enzymes, saccharides, oligosaccharides, polysaccharides, small molecule drugs, doxorubicin, aspirin, adriamycin, antibiotics, antimalarials, tamoxifen, dyes, organics, metals and nanoparticles.

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

5. The polymer matrix of claim 1 wherein the compatibilizing polymer comprises PEG.

6. The polymer matrix of claim 1 wherein the small functioning molecule comprises heparin.

7. The polymer matrix of claim 6 wherein the small functioning molecule comprises LMWH.

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

9. A method for formulating a functionalized polymer matrix comprising:

A. functionalizing a compatibilizing polymer with a small functioning molecule; and

B. administering said functionalized compatibilizing polymer into a matrix polymer.

10. The method of claim 9 wherein the step of administering said functionalized compatibilizing polymer into a matrix polymer is accomplished by a process comprising electrospinning.

11. The method of claim 9 wherein the matrix polymer is selected from the group consisting of PEO and PLGA.

12. The method of claim 9 wherein the compatibilizing polymer comprises PEG.

13. The method of claim 9 wherein the small functioning molecule comprises heparin.

14. The method of claim 13 wherein the small functioning molecule comprises LMWH.

15. The method of claim 9 wherein the compatibilizing polymer is further associated with a growth factor.