Peptide compositions for coating metal medical devices with vancomycin
View Patent ↗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 first molecules comprising:
(i) a first substrate-binding peptide comprising 6 to 40 amino acids and comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 55-112, 122-123, and 138-139, wherein the first substrate is a titanium or steel medical device and the first substrate-binding peptide has binding affinity for the medical device; and
(ii) a second substrate-binding peptide comprising 6 to 40 amino acids, wherein the second substrate is a vancomycin antibiotic and the second substrate-binding peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 124-126 and 131-137, and has binding affinity for the vancomycin antibiotic, wherein the first and second substrate-binding peptides are covalently linked; and
(b) a plurality of second molecules comprising:
the second substrate-binding peptide, wherein the second substrate-binding peptide is not covalently linked to the first substrate-binding peptide; and
(c) a plurality of the target molecule, vancomycin,
wherein each of the plurality of first and second molecules are covalently coupled to at least one interaction tag selected from the group consisting of a positively charged interaction tag and a negatively charged interaction tag, wherein the positively charged interaction tags interact with the negatively charged interaction tags to form a macromolecular network comprising the plurality of non-covalently coupled first and second molecules.
2. The composition of claim 1 , wherein the plurality of first molecules, the plurality of second molecules, 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 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.
5. The composition of claim 1 , wherein the first and second substrate-binding peptides are covalently linked by any one of 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”).
6. A method for coating a titanium or steel medical device, the method comprising contacting a composition with the metal-medical device, the composition comprising:
(a) a plurality of first molecules comprising:
(i) a first substrate-binding peptide comprising 6 to 40 amino acids and comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 55-112, 122-123, and 138-139, wherein the first substrate is the titanium or steel medical device and the first substrate-binding peptide has binding affinity for the medical device; and
(ii) a second substrate-binding peptide comprising 6 to 40 amino acids, wherein the second substrate is a vancomycin antibiotic and the second substrate-binding peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 124-126 and 131-137, and has binding affinity for the target molecule, wherein the first and second substrate-binding peptides are covalently linked; and
(b) a plurality of second molecules comprising:
(i) the second substrate-binding peptide, wherein the second substrate-binding peptide is not covalently linked to the first substrate-binding peptide; and
(c) a plurality of the target molecule, vancomycin,
wherein each of the plurality of first and second molecules are covalently coupled to at least one interaction tag selected from the group consisting of a positively charged interaction tag and a negatively charged interaction tag, wherein the positively charged interaction tags interact with the negatively charged interaction tags to form a macromolecular network comprising the plurality of non-covalently coupled first and second molecules.
7. The method of claim 6 , 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.
8. The method of claim 6 , wherein the first and second substrate-binding peptides are covalently linked by any one of 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”).