COATING COMPOSITIONS HAVING IMPROVED PERFORMANCE
The presently disclosed subject matter provides compositions comprising a first substrate-binding domain (a peptide or a polymer) having binding affinity for a tissue or a medical device, a second substrate-binding domain having binding affinity for a target molecule, and the target molecule. In some embodiments, the first and second substrate-binding domains are covalently linked. The first and second substrate-binding domains are covalently coupled to at least one hydrophobic interaction tag, negatively charged interaction tag, or positively charged interaction tag. When the substrate-binding domains are combined and coated onto the tissue or medical device, the hydrophobic interaction tags interact with each other and the charged interaction tags interact with the oppositely charged interaction tags or the oppositely charged substrate binding polymers, to form a macromolecular network of non-covalently coupled substrate-binding domains to load the target molecule onto the tissue or medical device.
1 . A composition comprising:
(a) a plurality of a first substrate-binding peptide comprising 3 to 40 amino acids, wherein the first substrate is a tissue or medical device and the first substrate-binding peptide has binding affinity for the tissue or medical device;
(b) a plurality of a second substrate-binding peptide comprising 3 to 40 amino acids, wherein the second substrate is a target molecule and the second substrate-binding peptide has binding affinity for the target molecule, wherein the first and second substrate-binding peptides are covalently linked; and
(c) a plurality of the target molecule,
wherein the plurality of covalently linked first and second substrate-binding peptides are covalently coupled to at least one interaction tag selected from the group consisting of a hydrophobic interaction tag, a positively charged interaction tag, and a negatively charged interaction tag, wherein the hydrophobic interaction tags interact with each other and the positively charged interaction tags interact with the negatively charged interaction tags to form a macromolecular network comprising the plurality of non-covalently coupled substrate-binding peptides.
2 . The composition of claim 1 , wherein the first substrate-binding peptide, the second substrate-binding peptide, and the target molecule are present in a pharmaceutically acceptable solution.
3 . The composition of claim 2 , wherein the pharmaceutically acceptable solution is in the form of a gel.
4 . The composition of claim 1 , wherein the first substrate tissue or medical device comprises a material selected from the group consisting of an animal tissue, an autologous tissue, an allogeneic tissue, a transplanted tissue, an organ tissue, a bone tissue, a skin tissue, a connective tissue, a muscle tissue, a nervous tissue, a polymer, a silk, a collagen, a synthetic polymer, a polyester, a polyurethane, a nylon, a polylactic acid, a polyglycolic acid, poly(lactic acid-co-glycolic acid), a plastic, a silicone material, a metal, a metal oxide, a non-metal oxide, a ceramic material, a calcium phosphate based material, a carbon-based material, a metallo-carbon composite, and combinations thereof.
5 . The composition of claim 1 , wherein the target molecule is selected from the group consisting of a cell, a protein, a polypeptide, a growth factor, a growth differentiation factor (GDF), a platelet derived growth factor (PDGF), a transforming growth factor (TGF), an osteogenic protein, a bone morphogenic protein (BMP), a hormone, a protein hormone, a parathyroid hormone (PTH), a drug, a drug carrier, an antibiotic, a vancomycin antibiotic, a steroid, a dexamethasone, and combinations thereof.
6 . The composition of claim 1 , wherein the charged interaction tag is selected from the group consisting of polylysine, polyarginine, polyamines, polyimines, polyethylamines, polyethylenimines (PEI), polyaspartic acid, polyglutamic acid, polystyrene sulfonate, poly(styrenesulfonic-maleic acid), and combinations and copolymers thereof.
7 . The composition of claim 1 , wherein the hydrophobic interaction tag is selected from the group consisting of fatty acids, undecanoic acid, poly-undecanoic acid, myristic acid, amino hexanoic acid, capric acid, lauric acid, palmitic acid, stearic acid, aromatic compounds, and combinations and copolymers thereof.
8 . The composition of claim 1 , wherein the first and second substrate-binding peptides are covalently linked by a peptide bond.
9 . The composition of claim 1 , wherein the first and second substrate-binding peptides are covalently linked through any one of the hydrophobic interaction tag, the charged interaction tag, amino acids, polymers, synthetic polymers, polyethers, poly(ethylene glycol) (“PEG”), a 10 unit polyethylene glycol (“P10”), and a 6 unit polyethylene glycol (“MP”).
10 . The composition of claim 1 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the hydrophobic interaction tag is poly-undecanoic acid, the hydrophobic interaction tag is covalently coupled to the first substrate binding peptide either directly, through a polyethylene glycol, or through an aminohexanoic acid, and the charged interaction tag is absent.
11 . The composition of claim 1 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the positively charged interaction tag is covalently coupled to a portion of the plurality of second substrate binding peptide, the negatively charged interaction tag is covalently coupled to a portion of the second substrate binding peptide, and the hydrophobic interaction tag is absent.
12 . The composition of claim 1 , wherein the first substrate medical device is a synthetic polymer, the second substrate target molecule is a growth factor, the hydrophobic interaction tag is poly-undecanoic acid, the first and second substrate binding peptides are covalently linked through the poly-undecanoic acid hydrophobic interaction tag, and the charged interaction tag is absent.
13 . The composition of claim 1 , wherein the first substrate medical device is a synthetic polymer, the second substrate target molecule is a growth factor, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the hydrophobic interaction tag is poly-undecanoic acid, the poly-undecanoic acid is covalently coupled to the second substrate binding peptides, and the charged interaction tag is absent.
14 . A method for coating a tissue or a medical device, the method comprising:
(a) contacting a composition with the tissue or medical device, the composition comprising:
(i) a plurality of a first substrate-binding peptide comprising 3 to 40 amino acids, wherein the first substrate is a tissue or medical device and the first substrate-binding peptide has binding affinity for the tissue or medical device;
(ii) a plurality of a second substrate-binding peptide comprising 3 to 40 amino acids, wherein the second substrate is a target molecule and the second substrate-binding peptide has binding affinity for the target molecule, wherein the first and second substrate-binding peptides are covalently linked; and
(iii) a plurality of the target molecule,
wherein the plurality of covalently linked first and second substrate-binding peptides are covalently coupled to at least one interaction tag selected from the group consisting of a hydrophobic interaction tag, a positively charged interaction tag, and a negatively charged interaction tag, wherein the hydrophobic interaction tags interact with each other and the positively charged interaction tags interact with the negatively charged interaction tags to form a macromolecular network comprising the plurality of non-covalently coupled substrate-binding peptides.
15 . The method of claim 14 , wherein the first substrate tissue or medical device comprises a material selected from the group consisting of an animal tissue, an autologous tissue, an allogeneic tissue, a transplanted tissue, an organ tissue, a bone tissue, a skin tissue, a connective tissue, a muscle tissue, a nervous tissue, a polymer, a silk, a collagen, a synthetic polymer, a polyester, a polyurethane, a nylon, a polylactic acid, a polyglycolic acid, poly(lactic acid-co-glycolic acid), a plastic, a silicone material, a metal, a metal oxide, a non-metal oxide, a ceramic material, a calcium phosphate based material, a carbon-based material, a metallo-carbon composite, and combinations thereof.
16 . The method of claim 14 , wherein the target molecule is selected from the group consisting of a cell, a protein, a polypeptide, a growth factor, a growth differentiation factor (GDF), a platelet derived growth factor (PDGF), a transforming growth factor (TGF), an osteogenic protein, a bone morphogenic protein (BMP), a hormone, a protein hormone, a parathyroid hormone (PTH), a drug, a drug carrier, an antibiotic, a vancomycin antibiotic, a steroid, a dexamethasone, and combinations thereof.
17 . The method of claim 14 , wherein the charged interaction tag is selected from the group consisting of polylysine, polyarginine, polyamines, polyimines, polyethylamines, polyethylenimines (PEI), polyaspartic acid, polyglutamic acid, polystyrene sulfonate, poly(styrenesulfonic-maleic acid), and combinations and copolymers thereof.
18 . The method of claim 14 , wherein the hydrophobic interaction tag is selected from the group consisting of fatty acids, undecanoic acid, poly-undecanoic acid, myristic acid, amino hexanoic acid, capric acid, lauric acid, palmitic acid, stearic acid, aromatic compounds, and combinations and copolymers thereof.
19 . The method of claim 14 , wherein the first and second substrate-binding peptides are covalently linked by a peptide bond.
20 . The method of claim 14 , wherein the first and second substrate-binding peptides are covalently linked through any one of the hydrophobic interaction tag, the charged interaction tag, amino acids, polymers, synthetic polymers, polyethers, poly(ethylene glycol) (“PEG”), a 10 unit polyethylene glycol (“P10”), and a 6 unit polyethylene glycol (“MP”).
21 . The method of claim 14 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the hydrophobic interaction tag is poly-undecanoic acid, the hydrophobic interaction tag is covalently coupled to the first substrate binding peptide either directly, through a polyethylene glycol, or through an aminohexanoic acid, and the charged interaction tag is absent.
22 . The method of claim 14 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the positively charged interaction tag is covalently coupled to a portion of the plurality of second substrate binding peptides, the negatively charged interaction tag is covalently coupled to a portion of the second substrate binding peptides, and the hydrophobic interaction tag is absent.
23 . The method of claim 14 , wherein the first substrate medical device is a synthetic polymer, the second substrate target molecule is a growth factor, the hydrophobic interaction tag is poly-undecanoic acid, the first and second substrate binding peptides are covalently linked through the poly-undecanoic acid hydrophobic interaction tag, and the charged interaction tag is absent.
24 . The method of claim 14 , wherein the first substrate medical device is a synthetic polymer, the second substrate target molecule is a growth factor, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the hydrophobic interaction tag is poly-undecanoic acid, the poly-undecanoic acid is covalently coupled to the second substrate binding peptides, and the charged interaction tag is absent.
25 . A coated medical device, wherein at least a portion of the medical device is coated with a composition comprising:
(a) a plurality of a first substrate-binding peptide comprising 3 to 40 amino acids, wherein the first substrate is a tissue or medical device and the first substrate-binding peptide has binding affinity for the tissue or medical device;
(b) a plurality of a second substrate-binding peptide comprising 3 to 40 amino acids, wherein the second substrate is a target molecule and the second substrate-binding peptide has binding affinity for the target molecule, wherein the first and second substrate-binding peptides are covalently linked; and
(c) a plurality of the target molecule,
wherein the plurality of covalently linked first and second substrate-binding peptides are covalently coupled to at least one interaction tag selected from the group consisting of a hydrophobic interaction tag, a positively charged interaction tag, and a negatively charged interaction tag, wherein the hydrophobic interaction tags interact with each other and the positively charged interaction tags interact with the negatively charged interaction tags to form a macromolecular network comprising the plurality of non-covalently coupled substrate-binding peptides.
26 . The coated medical device of claim 25 , wherein the first substrate tissue or medical device comprises a material selected from the group consisting of an animal tissue, an autologous tissue, an allogeneic tissue, a transplanted tissue, an organ tissue, a bone tissue, a skin tissue, a connective tissue, a muscle tissue, a nervous tissue, a polymer, a silk, a collagen, a synthetic polymer, a polyester, a polyurethane, a nylon, a polylactic acid, a polyglycolic acid, poly(lactic acid-co-glycolic acid), a plastic, a silicone material, a metal, a metal oxide, a non-metal oxide, a ceramic material, a calcium phosphate based material, a carbon-based material, a metallo-carbon composite, and combinations thereof.
27 . The coated medical device of claim 25 , wherein the target molecule is selected from the group consisting of a cell, a protein, a polypeptide, a growth factor, a growth differentiation factor (GDF), a platelet derived growth factor (PDGF), a transforming growth factor (TGF), an osteogenic protein, a bone morphogenic protein (BMP), a hormone, a protein hormone, a parathyroid hormone (PTH), a drug, a drug carrier, an antibiotic, a vancomycin antibiotic, a steroid, a dexamethasone, and combinations thereof.
28 . The coated medical device of claim 25 , wherein the charged interaction tag is selected from the group consisting of polylysine, polyarginine, polyamines, polyimines, polyethylamines, polyethylenimines (PEI), polyaspartic acid, polyglutamic acid, polystyrene sulfonate, poly(styrenesulfonic-maleic acid), and combinations and copolymers thereof.
29 . The coated medical device of claim 25 , wherein the hydrophobic interaction tag is selected from the group consisting of fatty acids, undecanoic acid, poly-undecanoic acid, myristic acid, amino hexanoic acid, capric acid, lauric acid, palmitic acid, stearic acid, aromatic compounds, and combinations and copolymers thereof.
30 . The coated medical device of claim 25 , wherein the first and second substrate-binding peptides are covalently linked by a peptide bond.
31 . The coated medical device of claim 25 , wherein the first and second substrate-binding peptides are covalently linked through any one of the hydrophobic interaction tag, the charged interaction tag, amino acids, polymers, synthetic polymers, polyethers, poly(ethylene glycol) (“PEG”), a 10 unit polyethylene glycol (“P10”), and a 6 unit polyethylene glycol (“MP”).
32 . The coated medical device of claim 25 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the hydrophobic interaction tag is poly-undecanoic acid, the hydrophobic interaction tag is covalently coupled to the first substrate binding peptide either directly, through a polyethylene glycol, or through an aminohexanoic acid, and the charged interaction tag is absent.
33 . The coated medical device of claim 25 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the positively charged interaction tag is covalently coupled to a portion of the plurality of second substrate binding peptides, the negatively charged interaction tag is covalently coupled to a portion of the second substrate binding peptides, and the hydrophobic interaction tag is absent.
34 . The coated medical device of claim 25 , wherein the first substrate medical device is a synthetic polymer, the second substrate target molecule is a growth factor, the hydrophobic interaction tag is poly-undecanoic acid, the first and second substrate binding peptides are covalently linked through the poly-undecanoic acid hydrophobic interaction tag, and the charged interaction tag is absent.
35 . The coated medical device of claim 25 , wherein the first substrate medical device is a synthetic polymer, the second substrate target molecule is a growth factor, the first and second substrate binding peptides are covalently linked through a polyethylene glycol, the hydrophobic interaction tag is poly-undecanoic acid, the poly-undecanoic acid is covalently coupled to the second substrate binding peptides, and the charged interaction tag is absent.