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 polymer having a net negative or a net positive charge, wherein the first substrate is a tissue or medical device and the first substrate-binding polymer has binding affinity for the tissue or medical device;
(b) a plurality of a second substrate-binding peptide of 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 substrate-binding polymer and the second substrate-binding peptide are not covalently linked; and
(c) a plurality of the target molecule,
wherein the plurality of second substrate-binding peptides are covalently coupled to at least one net positively or net negatively charged interaction tag, wherein the charge of the interaction tag is opposite to the charge of the first substrate-binding polymer, wherein each of the plurality of first substrate-binding polymers and second substrate-binding peptides is optionally covalently coupled to a hydrophobic interaction tag, wherein the charged interaction tag interacts with the first substrate-binding polymer and the optional hydrophobic interaction tags interact with each other to form a macromolecular network comprising the plurality of non-covalently coupled first substrate-binding polymers and second 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 autologous tissue, an allogeneic tissue, a transplanted tissue, an organ tissue, a bone tissue, a skin tissue, a connective tissue, a muscle tissue, a polymer, a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a ceramic material, a calcium phosphate based material, 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 first substrate-binding polymer having a net negative charge is selected from the group consisting of polystyrene sulfonate, polyglutamic acid, polylactic acid, polyglycolic acid, poly(lactic acid-co-glycolic acid), heparin, and combinations and copolymers thereof.
7 . The composition of claim 1 , wherein the first substrate-binding polymer having a net positive charge is selected from the group consisting of polyimines, polyamines, polyethylenimines, polyethylamines, and polylysine, and combinations and copolymers thereof.
8 . 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.
9 . 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.
10 . The composition of claim 1 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first substrate binding polymer having a positive charge is polyethylenimine, the negatively charged interaction tag covalently coupled to the second substrate binding peptide is polyglutamic acid or polyaspartic acid, the charged interaction tag is coupled to the substrate binding peptide directly or coupled through a polyethylene glycol, and the optional hydrophobic interaction tag is absent.
11 . 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 polymer having a net negative or a net positive charge, wherein the first substrate is a tissue or medical device and the first substrate-binding polymer has binding affinity for the tissue or medical device;
(ii) a plurality of a second substrate-binding peptide of 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 substrate-binding polymer and the second substrate-binding peptide is not covalently linked; and
(iii) a plurality of the target molecule,
wherein the plurality of second substrate-binding peptides are covalently coupled to at least one net positively or net negatively charged interaction tag, wherein the charge of the interaction tag is opposite to the charge of the first substrate-binding polymer, wherein each of the plurality of first substrate-binding polymers and second substrate-binding peptides is optionally covalently coupled to a hydrophobic interaction tag, wherein the charged interaction tag interacts with the first substrate-binding polymer and the optional hydrophobic interaction tags interact with each other to form a macromolecular network comprising the plurality of non-covalently coupled first substrate-binding polymers and second substrate-binding peptides.
12 . The method of claim 11 , wherein the first substrate tissue or medical device comprises a material selected from the group consisting of 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 polymer, a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a ceramic material, a calcium phosphate based material, and combinations thereof.
13 . The method of claim 11 , 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.
14 . The method of claim 11 , wherein the first substrate-binding polymer having a net negative charge is selected from the group consisting of polystyrene sulfonate, polyglutamic acid, polylactic acid, polyglycolic acid, poly(lactic acid-co-glycolic acid), heparin, and combinations and copolymers thereof.
15 . The method of claim 11 , wherein the first substrate-binding polymer having a net positive charge is selected from the group consisting of polyimines, polyamines, polyethylenimines, polyethylamines, and polylysine, and combinations and copolymers thereof.
16 . The method of claim 11 , 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.
17 . The method of claim 11 , 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.
18 . The method of claim 11 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first substrate binding polymer having a positive charge is polyethylenimine, the negatively charged interaction tag covalently coupled to the second substrate binding peptide is polyglutamic acid or polyaspartic acid, the charged interaction tag is coupled to the substrate binding peptide directly or coupled through a polyethylene glycol, and the optional hydrophobic interaction tag is absent.
19 . 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 polymer having a net negative or a net positive charge, wherein the first substrate is a tissue or medical device and the first substrate-binding polymer has binding affinity for the tissue or medical device;
(b) a plurality of a second substrate-binding peptide of 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 substrate-binding polymer and the second substrate binding peptide are not covalently linked; and
(c) a plurality of the target molecule,
wherein the plurality of second substrate-binding peptides are covalently coupled to at least one net positively or net negatively charged interaction tag, wherein the charge of the interaction tag is opposite to the charge of the first substrate-binding polymer, wherein each of the plurality of first substrate-binding polymers and second substrate-binding peptides is optionally covalently coupled to a hydrophobic interaction tag, wherein the charged interaction tag interacts with the first substrate-binding polymer and the optional hydrophobic interaction tags interact with each other to form a macromolecular network comprising the plurality of non-covalently coupled first substrate-binding polymers and second substrate-binding peptides.
20 . The coated medical device of claim 19 , wherein the first substrate tissue or medical device comprises a material selected from the group consisting of 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 polymer, a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a ceramic material, a calcium phosphate based material, and combinations thereof.
21 . The coated medical device of claim 19 , 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.
22 . The coated medical device of claim 19 , wherein the first substrate-binding polymer having a net negative charge is selected from the group consisting of polystyrene sulfonate, polyglutamic acid, polylactic acid, polyglycolic acid, poly(lactic acid-co-glycolic acid), heparin, and combinations and copolymers thereof.
23 . The coated medical device of claim 19 , wherein the first substrate-binding polymer having a net positive charge is selected from the group consisting of polyimines, polyamines, polyethylenimines, polyethylamines, and polylysine, and combinations and copolymers thereof.
24 . The coated medical device of claim 19 , 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.
25 . The coated medical device of claim 19 , 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 thereof.
26 . The coated medical device of claim 19 , wherein the first substrate is a metal medical device, the second substrate target molecule is vancomycin, the first substrate binding polymer having a positive charge is polyethylenimine, the negatively charged interaction tag covalently coupled to the second substrate binding peptide is polyglutamic acid or polyaspartic acid, the charged interaction tag is coupled to the substrate binding peptide directly or coupled through a polyethylene glycol, and the optional hydrophobic interaction tag is absent.