Hydroxyapatite-targeting poly(ethylene glycol) and related polymers
View Patent ↗Isolatable, hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are provided. The polymeric structure includes a linear or branched water-soluble and non-peptidic polymer backbone, such as a PEG backbone, having at least two termini, a first terminus being covalently bonded to a hydroxyapatite-targeting moiety, such as a bisphosphonate, and a second terminus covalently bonded to a chemically reactive group, wherein said chemically reactive group is protected or unprotected. Methods of preparing and using hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are also provided.
1. A method for attaching a hydroxyapatite-targeting water-soluble polymer to a surface or device, said method comprising the steps of:
a) providing a water-soluble polymer comprising at one terminus, a hydroxyapatite-targeting moiety, and
b) binding the water-soluble polymer from step (a) with a hydroxyapatite- or calcium phosphate-coated prosthetic or drug delivery device or surface under conditions effective to promote said binding.
2. The method of claim 1 , wherein the water-soluble polymer is selected from the group consisting of poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(vinylpyrolidone), poly(hydroxypropylmethacrylamide), poly(α-hydroxy acid), poly(vinyl alcohol), polyphosphazene, polyoxazoline, and copolymers and terpolymers thereof.
3. The method of claim 2 , wherein the water-soluble polymer is a poly(alkylene glycol).
4. The method of claim 3 , wherein the water-soluble polymer is a poly(ethylene glycol).
5. The method of claim 4 , wherein the poly(ethylene glycol) is linear.
6. The method of claim 4 , wherein the poly(ethylene glycol) is branched.
7. The method of claim 4 , wherein the water-soluble polymer has a molecular weight ranging from about 100 daltons to about 100,000 daltons.
8. The method of claim 7 , wherein the water-soluble polymer has a molecular weight ranging from about 6,000 daltons to about 80,000 daltons.
9. The method of claim 1 , wherein the hydroxyapatite-targeting moiety is selected from the group consisting of tetracycline, calcein, bisphosphonates, polyaspartic acid, polyglutamic acid, and aminophosphosugars.
10. The method of claim 1 , wherein the hydroxyapatite-targeting moiety is a bisphosphonate.
11. The method of claim 10 , wherein the bisphosphonate is selected from the group consisting of etidronate, alendronate, and 3-amino-1-hydroxypropane-1-1-diphosphonic acid (AHPDP).
12. The method of claim 10 , wherein the water-soluble polymer is a poly(ethylene glycol).
13. The method of claim 1 , wherein the water-soluble polymer comprises at a second terminus, a biologically active agent.
14. The method of claim 1 , wherein the water-soluble polymer comprises at a second terminus, a protecting group.
15. The method of claim 14 , wherein the protecting group is protected hydroxyl.
16. The method of claim 1 , wherein said binding comprises incubating the hydroxyapatite or calcium phosphate coated prosthetic or drug delivery device or surface with a solution comprising the hydroxyapatite-targeting water-soluble polymer under conditions effective to promote binding thereto.
17. A hydroxyapatite- or calcium phosphate-coated prosthetic or drug delivery device or surface comprising a water-soluble polymer having at one terminus, a hydroxyapatite-targeting moiety, bound thereto.