Reinforced adhesive complex coacervates and methods of making and using thereof
Described herein is the synthesis of reinforced adhesive complex coacervates and their use thereof. The reinforced adhesive complex coacervates are composed of (a) at least one polycation, (b) at least one polyanion, and (c) a reinforcing component. The adhesive complex coacervates described herein can be subsequently cured to produce strong, cohesive adhesives. The reinforced adhesive complex coacervates have several desirable features when compared to conventional adhesives. The reinforced adhesive complex coacervates are effective in wet or underwater applications. The reinforced adhesive complex coacervates described herein, being phase separated from water, can be applied underwater without dissolving or dispersing into the water. The reinforced adhesive complex coacervates have numerous biological applications as bioadhesives and bioactive delivery devices. In particular, the reinforced adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, wet tissues in physiological conditions.
1. A method for inhibiting blood flow in a blood vessel of a subject comprising introducing as associative liquid adhesive complex coacervate into the vessel, wherein the complex coacervate comprises (a) at least one polycation, (b) at least one polyanion, and (c) a reinforcing component.
2. The method of claim 1 , wherein the polycation comprises a polyamino compound.
3. The method of claim 1 , wherein the polycation comprises a polysaccharide, a natural protein, a recombinant protein, or a synthetic polyamine.
4. The method of claim 1 , wherein the polycation comprises an alkylamino group, a heteroaryl group, a guanidinyl group, or an aromatic group substituted with one or more amino groups.
5. The method of claim 1 , wherein the polycation comprises a natural protein.
6. The method of claim 5 , wherein the natural protein comprises one or more guanidinyl groups.
7. The method of claim 1 , 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.
8. The method of claim 7 , wherein R 1 , R 2 , and R 3 are methyl, X is O, and m is 3.
9. The method of claim 1 , wherein the polyanion comprises two or more sulfate, sulfonate, carboxylate, borate, boronate, phosphonate, or phosphate groups.
10. The method of claim 1 , wherein the polyanion comprises a polyphosphate.
11. The method of claim 10 , wherein the polyphosphate comprises a natural polymer or a synthetic polymer.
12. The method of claim 10 , wherein the polyphosphate comprises a polyacrylate comprising one or more pendant phosphate groups.
13. The method of claim 1 , 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 an anionic group or a group that can be converted to an anionic group,
or the pharmaceutically-acceptable salt thereof.
14. The method of claim 13 , wherein Z is sulfate, sulfonate, carboxylate, borate, boronate, a substituted or unsubstituted phosphate, or a phosphonate.
15. The method of claim 1 , wherein the polyanion comprises a polymer comprising at least one fragment comprising the formula II
wherein R 4 is hydrogen or an alkyl group, and n is from 1 to 10, or the pharmaceutically-acceptable salt thereof.
16. The method of claim 15 , wherein R 4 is methyl and n is 2.
17. The method of claim 1 , wherein the reinforcing component comprises a particle, wherein the particle comprises a metal oxide, a ceramic particle, a silica particle, or a water insoluble inorganic salt.
18. The method of claim 1 , wherein the reinforcing component comprises a fiber.
19. The method of claim 1 , wherein the reinforcing component comprises a metal oxide particle.
20. The method of claim 1 , wherein the reinforcing component comprises a metal particle.
21. The method of claim 20 , wherein the metal particle is platinum, gold, or tantalum.
22. The method of claim 1 , wherein the polycation comprises a natural protein comprising one or more guanidinyl groups, the polyanion comprises a polyphosphate, and the reinforcing component comprises a metal particle.
23. The method of claim 1 , wherein the associative liquid adhesive complex coacervate further comprises a bioactive agent selected from the group consisting of a nucleic acid, an antibiotic, a pain reliever, an immune modulator, a growth factor, an enzyme inhibitor, a hormone, a mediator, a messenger molecule, a cell signaling molecule, a receptor agonist, and a receptor antagonist, wherein the bioactive agent is encapsulated in the associative liquid adhesive complex coacervate.