Copolymers and methods of use thereof
Copolymers, such as block copolymers, having at least one block that is a random copolymer of ε-caprolactone and α-carboxy-ε-caprolactone are described. Also described are methods of using such copolymers, such as, for example, in medical devices.
1. A polymer of formula (I):
wherein:
R 1 is selected from an alkyl, an acyl and an aryl;
each R 2 is independently selected from —H and —COOH;
R 3 is selected from —H, an alkyl and an aryl;
m is an integer from about 20 to about 200; and
n is an integer from about 200 to about 2000;
wherein at least one of the R 2 substituents is —H and at least one of the R 2 substituents is —COOH.
2. The polymer of claim 1 , wherein R 1 is an alkyl.
3. The polymer of claim 2 , wherein R 1 is methyl.
4. The polymer of claim 1 , wherein m is an integer from 40 to 140.
5. The polymer of claim 1 , wherein n is an integer from 500 to 1000.
6. The polymer of claim 1 , wherein from about 70-95% of R 2 substituents are —H and from about 5-30% of R 2 substituents are —COOH.
7. The polymer of claim 1 , wherein R 3 is —H.
8. A composition comprising the polymer of claim 1 and at least one compound covalently attached to the polymer.
9. The composition of claim 8 , wherein the at least one compound crosslinks a plurality of polymers.
10. The composition of claim 9 , wherein the at least one compound is covalently attached to one or more —COOH moieties.
11. The composition of claim 8 , wherein the compound comprises a hydrophilic polymer.
12. The composition of claim 11 , wherein the compound comprises poly(ethylene glycol).
13. The composition of claim 12 , wherein the compound is poly(ethylene glycol)-dihydrazide.
14. A medical device comprising the polymer of claim 1 .
15. The medical device of claim 14 , wherein the device is a cardiovascular stent, a cardiac patch, or a catheter.
16. A block copolymer comprising:
at least one hydrophilic polymer block; and
at least one block comprising a random copolymer of ε-caprolactone and α-carboxy-ε-caprolactone.
17. The block copolymer of claim 16 , wherein at least one hydrophilic polymer block comprises poly(ethylene glycol), poly(propylene glycol), poly(vinylpyrrolidone), or a poly(amino acid).
18. The block copolymer of claim 17 , wherein the at least one hydrophilic polymer block comprises poly(ethylene glycol).
19. The block copolymer of claim 18 , wherein the poly(ethylene glycol) polymer block comprises methoxy-poly(ethylene glycol).
20. The block copolymer of claim 18 , wherein the poly(ethylene glycol) polymer block has a molecular weight of about 1000-8000 Da.
21. The block copolymer of claim 16 , wherein the random copolymer of ε-caprolactone and α-carboxy-ε-caprolactone comprises about 70-95% caprolactone moieties and about 5-30% α-carboxy-ε-caprolactone moieties.
22. A composition comprising the block copolymer of claim 16 and at least one compound covalently attached to the block copolymer.
23. The composition of claim 22 , wherein the at least one compound crosslinks a plurality of polymers.
24. The composition of claim 23 , wherein the at least one compound is covalently linked to the α-carboxy groups of α-carboxy-ε-caprolactone.
25. A medical device comprising the block copolymer of claim 16 .
26. A method of making a block copolymer comprising:
providing a hydrophilic polymer comprising a terminal hydroxyl group;
reacting said hydrophilic polymer with caprolactone and a catalyst under conditions sufficient to effect ring-opening polymerization of the caprolactone, to form a block copolymer comprising a hydrophilic polymer block and at least one caprolactone block; and
carboxylating the α-carbon of at least one caprolactone moiety.
27. The method of claim 26 , wherein the hydrophilic polymer comprises poly(ethylene glycol), poly(propylene glycol), poly(vinylpyrrolidone), or a poly(amino acid).
28. The method of claim 27 , wherein the hydrophilic polymer comprises poly(ethylene glycol).
29. The method of claim 28 , wherein the poly(ethylene glycol) polymer block comprises methoxy-poly(ethylene glycol).
30. The method of claim 28 , wherein the poly(ethylene glycol) polymer block has a molecular weight of about 1000-8000 Da.
31. The method of claim 26 , wherein the carboxylating step comprises reacting the block copolymer with a base and carbon dioxide.