Simple coacervates and methods of use thereof
Described herein is the synthesis of adhesive from simple adhesive coacervates and their uses thereof. The adhesives are produced by (a) preparing a solution comprising (1) a polyelectrolyte, wherein the polyelectrolyte comprises a polyanion or polycation but not a combination thereof, the polyeletrolyte comprises at least one crosslinking group, and (2) a sufficient amount of a complimentary counterion to produce a simple adhesive coacervate; and (b) crosslinking the simple adhesive coacervate to produce the adhesive. The adhesives have numerous medical and non-medical applications.
1. A method for producing an adhesive in a subject comprising
(a) introducing into the subject a simple coacervate comprising a polyelectrolyte, wherein the polyelectrolyte comprises a polyanion or polycation but not a combination thereof, and the polyelectrolyte comprises at least one crosslinking group capable of covalently crosslinking with itself, and (2) a sufficient amount of a complimentary multivalent cation or multivalent anion to produce the simple coacervate; and
(b) covalently crosslinking the polyelectrolyte in the simple coacervate to produce the adhesive in the subject.
2. The method of claim 1 for closing or sealing a puncture in an internal tissue or membrane of the subject comprising (a) applying the simple coacervate to the puncture and (b) covalently crosslinking the polyelectrolyte in the simple coacervate.
3. The method of claim 1 for closing or sealing a puncture in internal tissue or membrane in the subject by adhering a scaffold to or within the puncture with the simple coacervate and subsequently covalently crosslinking the polyelectrolyte in the simple coacervate.
4. The method of claim 1 wherein the simple coacervate is introduced into a blood vessel and subsequently covalently crosslinking the polyelectrolyte in the simple coacervate to partially or completely block the vessel.
5. The method of claim 1 wherein the simple coacervate is applied to a fractured bone and subsequently covalently crosslinking the polyelectrolyte in the simple coacervate to repair the fractured bone.
6. The method of claim 1 for adhering a bone-tissue scaffold to a bone of the subject comprising (a) contacting the bone and/or tissue with the simple coacervate, (b) applying the bone-tissue scaffold to the bone and tissue, and (c) covalently crosslinking the polyelectrolyte in the simple coacervate.
7. The method of claim 1 for method for securing a dental implant in the subject, comprising (a) applying to an oral substrate and/or dental implant the simple coacervate, (b) attaching the dental implant to the substrate, and (c) covalently crosslinking the polyelectrolyte in the simple coacervate.
8. The method of claim 1 for treating an ocular wound in a subject comprising applying to the wound the simple coacervate and subsequently covalently crosslinking the polyelectrolyte in the simple coacervate.
9. The method of claim 1 , wherein the polyelectrolyte is a polyanion.
10. The method of claim 9 , wherein the polyanion comprises a synthetic or naturally-occurring polymer comprising one or more sulfate, sulfonate, carboxylate, borate, boronate, phosphonate, phosphate groups, or any combination thereof.
11. The method of claim 9 , wherein the polyanion comprises a polysaccharide, a protein, or a synthetic polypeptide.
12. The method of claim 9 , wherein the polyanion comprises an inorganic polyphosphate compound.
13. The method of claim 9 , wherein the polyanion comprises a polymer comprising at least one fragment comprising the formula X
wherein R 4 is hydrogen or an alkyl group;
n is from 1 to 10;
Y is oxygen, sulfur, or NR 30 , wherein R 30 is hydrogen, an alkyl group, or an aryl group;
Z is sulfate, sulfonate, carboxylate, borate, boronate, a substituted or unsubstituted phosphate, or a phosphonate,
or the pharmaceutically-acceptable salt thereof.
14. The method of claim 9 , wherein the complimentary multivalent cation is Mg +2 .
15. The method of claim 1 , wherein the polyelectrolyte is a polycation.
16. The method of claim 15 , wherein the polycation comprises a synthetic or naturally-occurring polymer comprising one or more primary, secondary, or tertiary amino groups, an alkylamino group, a heterocyclic amine, or an aromatic amine.
17. The method of claim 15 , wherein the polycation comprises a polysaccharide, a protein, a synthetic polyamine, or a synthetic polypeptide.
18. The method of claim 15 , wherein the polycation comprises a polymer comprising at least one fragment comprising the formula I
wherein R 1 , R 2 , and R 3 are, independently, hydrogen or an alkyl group,
X is oxygen or NR 5 , where R 5 is hydrogen or an alkyl group, and
m is from 1 to 10,
or the pharmaceutically-acceptable salt thereof.
19. The method of claim 15 , wherein the polycation comprises one or more pendant guanidinyl groups.
20. The method of claim 15 , wherein the complimentary multivalent anion is a sulfate, a borate, a substituted or unsubstituted phosphate, or a phosphonate.
21. The method of claim 1 , wherein the polyelectrolyte comprises electrostatically associated block copolymers, wherein the block co-polymers comprise alternating polycationic blocks and polyanionic blocks.
22. The method of claim 1 , wherein the crosslinking group is pendant to a polymer backbone of the polycation or polyanion.
23. The method of claim 1 , wherein the crosslinking group comprises an actinically crosslinkable group.
24. The method of claim 22 , wherein the actinically crosslinkable comprises an acryloyl group or a methacryloyl group.
25. The method of claim 1 , wherein the simple coacervate further comprises one or more bioactive agents.
26. The method of claim 1 , wherein the simple coacervate further comprises one or more contrast agents.
27. The method of claim 1 , wherein the simple coacervate further comprises a polymerizable monomer, a water-insoluble filler, or a combination thereof.
28. The method of claim 1 , wherein the simple coacervate modifies one or more surface properties in the subject.
29. The method of claim 27 , wherein the simple coacervate promotes biomolecules attachment or cell attachment in the subject.
30. A method for modifying one or more surface properties of a substrate, the method comprising
(a) applying on the surface of the substrate a simple coacervate comprising a polyelectrolyte, wherein the polyelectrolyte comprises a polyanion or polycation but not a combination thereof, and the polyelectrolyte comprises at least one crosslinking group capable of covalently crosslinking with itself, and (2) a sufficient amount of a complimentary multivalent cation or multivalent anion to produce the simple coacervate; and
(b) covalently crosslinking the polyelectrolyte in the simple coacervate on the surface of the substrate to modify one or more surface properties of the substrate.
31. The method of claim 26 , wherein the surface property is wettability, corrosion resistance, anti-fouling, or promotion of specific interactions on the surface of the substrate.
32. The method of claim 26 , wherein the substrate is a metal substrate, a foil, a fiber, a tape, a cloth, coral, or a device that can be implanted in a subject.
33. A method for adhering two substrates together, the method comprising
(a) applying on the surface of a first substrate a simple coacervate comprising a polyelectrolyte, wherein the polyelectrolyte comprises a polyanion or polycation but not a combination thereof, and the polyelectrolyte comprises at least one crosslinking group capable of covalently crosslinking with itself, and (2) a sufficient amount of a complimentary multivalent cation or multivalent anion to produce the simple coacervate;
(b) applying the second substrate to the first substrate, wherein the second substrate is in contact with the simple coacervate; and
(c) covalently crosslinking the polyelectrolyte in the simple coacervate on the surface of the substrate to adhere the first substrate to the second substrate.
34. A simple coacervate comprising (1) a polycation comprising one or more guanidinium groups, wherein the polycation comprises at least one crosslinking group capable of covalently crosslinking with itself, and (2) a sufficient amount of multivalent anion to produce the simple coacervate.
35. The simple coacervate of claim 34 , wherein the multivalent anion is sulfate or phosphate.
36. A simple coacervate comprising (1) a polyanion comprising a polyphosphate compound comprising at least one phosphate group pendant to the polymer backbone and/or at least one phosphate group incorporated in the polymer backbone, wherein the polyanion comprises at least one crosslinking group capable of covalently crosslinking with itself, and (2) a sufficient amount of multivalent cation to produce the simple coacervate.
37. The simple coacervate of claim 36 , wherein the multivalent cation is Mg +2 .
38. The simple coacervate of claim 34 , wherein the polycation comprises a synthetic or naturally-occurring polymer comprising one or more primary, secondary, or tertiary amino groups, an alkylamino group, a heterocyclic amine, or an aromatic amine.
39. The simple coacervate of claim 34 , wherein the polycation comprises a polysaccharide, a protein, a synthetic polyamine, or a synthetic polypeptide.
40. The simple coacervate of claim 34 , wherein the polycation comprises a polymer comprising at least one fragment comprising the formula I
wherein R 1 , R 2 , and R 3 are, independently, hydrogen or an alkyl group,
X is oxygen or NR 5 , where R 5 is hydrogen or an alkyl group, and
m is from 1 to 10,
or the pharmaceutically-acceptable salt thereof.
41. The simple coacervate of claim 34 , wherein the complimentary multivalent anion is a sulfate, a borate, a substituted or unsubstituted phosphate, or a phosphonate.
42. The simple coacervate of claim 34 , wherein the crosslinking group comprises an actinically crosslinkable group.
43. The simple coacervate of claim 42 , wherein the actinically crosslinkable group comprises an acryloyl group or a methacryloyl group.
44. The simple coacervate of claim 34 , wherein the simple coacervate further comprises one or more bioactive agents.
45. The simple coacervate of claim 34 , wherein the simple coacervate further comprises one or more contrast agents.
46. The simple coacervate of claim 34 , wherein the simple coacervate further comprises a polymerizable monomer, a water-insoluble filler, or a combination thereof.
47. The simple coacervate of claim 36 , wherein the polyphosphate compound comprises a polymer comprising at least one fragment comprising the formula X
wherein R 4 is hydrogen or an alkyl group;
n is from 1 to 10;
Y is oxygen, sulfur, or NR 30 , wherein R 30 is hydrogen, an alkyl group, or an aryl group;
Z is a substituted or unsubstituted phosphate,
or the pharmaceutically-acceptable salt thereof.
48. The simple coacervate of claim 36 , wherein the polyphosphate compound comprises a polymer comprising at least one fragment comprising the formula II
wherein R 4 is hydrogen or an alkyl group,
n is from 1 to 10, and
R 40 is hydrogen, an alkyl group, or an aryl group.
49. The simple coacervate of claim 48 , wherein R 4 is methyl, R 40 is hydrogen, n is 2.
50. The simple coacervate of claim 36 , wherein the polyphosphate compound comprises an inorganic polyphosphate compound.
51. The simple coacervate of claim 36 , wherein the crosslinking group comprises an actinically crosslinkable group.
52. The simple coacervate of claim 51 , wherein the actinically crosslinkable group comprises an acryloyl group or a methacryloyl group.
53. The simple coacervate of claim 36 , wherein the simple coacervate further comprises one or more bioactive agents.
54. The simple coacervate of claim 36 , wherein the simple coacervate further comprises one or more contrast agents.
55. The simple coacervate of claim 36 , wherein the simple coacervate further comprises a polymerizable monomer, a water-insoluble filler, or a combination thereof.