Biocompatible phase invertible proteinaceous compositions and methods for making and using the same
Biocompatible phase invertible proteinaceous compositions and methods for making and using the same are provided. The subject phase invertible compositions are prepared by combining a crosslinker and a proteinaceous substrate. The proteinaceous substrate includes one or more proteins and a polyamine, where the polyamine and a proteinaceous substrate are present in synergistic viscosity enhancing amounts, and may also include one or more of: a carbohydrate, a tackifying agent, a plasticizer, or other modification agent. In certain embodiments, the crosslinker is a heat-treated dialdehyde, e.g., heat-treated glutaraldehyde. Also provided are kits for use in preparing the subject compositions. The subject compositions, kits and systems find use in a variety of different applications.
1. A method for treating a host, the method comprising delivering a phase invertible composition to a target location, the phase invertible composition produced by combining:
a substrate comprising a polyamine and a proteinaceous material in a weight ratio of polyamine to proteinaceous material being in the range from 1:10 to 1:40, wherein the combination of the polyamine and the proteinaceous material has a viscosity which is greater than that of either the polyamine or the proteinaceous material alone; and
a crosslinking agent, wherein the crosslinking agent causes the polyamine and the proteinaceous material to crosslink and the polyamine and the proteinaceous material crosslink in the presence of the crosslinking agent, wherein the crosslinking agent is exposed to radiation,
wherein the substrate has a kinematic viscosity of about 70 to 200 centistokes,
wherein the proteinaceous material is selected from the group consisting of albumin, elastin, fibrin and soluble and insoluble forms of collagen and combinations thereof, and
wherein the crosslinking agent comprises a macromolecular crosslinking agent comprising a reaction product of an excess of a liquid aldehyde cross linking agent and a glycosaminoglycan.
2. The method of claim 1 , wherein the radiation sterilizes the crosslinking agent.
3. The method of claim 1 , wherein the radiation comprises gamma radiation.
4. The method of claim 1 , wherein the radiation comprises electron beam radiation.
5. The method of claim 1 , wherein the polyamine is a polyalkyleneimine.
6. The method of claim 5 , wherein the polyalkyleneimine is a polyethyleneimine.
7. The method of claim 6 , wherein the polyethyleneimine is a branched polyethyleneimine.
8. The method of claim 1 , wherein the substrate further comprises a carbohydrate.
9. The method of claim 8 , wherein the carbohydrate is chitosan.
10. The method of claim 9 , wherein the substrate comprises about 0.1% (w/w) to about 5% (w/w) chitosan.
11. The method of claim 9 , wherein the substrate comprises about 0.1% (w/w) to about 0.3% (w/w) chitosan.
12. The method of claim 9 , wherein the substrate comprises about 0.16% (w/w) chitosan.
13. The method of claim 1 , wherein the crosslinking agent comprises an aldehyde.
14. The method of claim 13 , wherein the aldehyde is glutaraldehyde.
15. The method of claim 14 , wherein the glutaraldehyde is heat stabilized.
16. The method of claim 1 , wherein the glycosaminoglycan is hyaluronan.
17. The method of claim 1 , wherein the viscosity of the substrate approximates that of the crosslinking agent.
18. The method of claim 17 , wherein the crosslinking agent further comprises a viscosity modifying agent.
19. The method of claim 1 , wherein the substrate further comprises an agent selected from the group consisting of a tackifying agent, and a plasticizing agent.
20. The method of claim 1 , wherein the crosslinking agent further comprises an agent selected from the group consisting of a tackifying agent, and a plasticizing agent.
21. The method of claim 8 , wherein the weight ratio of the carbohydrate to proteinaceous material is about 1:130 to 1:400.
22. The method of claim 1 , wherein the polyamine has an average molecular weight from about 500 to about 1 million Daltons.
23. The method of claim 1 , wherein the substrate comprises about 0.5 to about 4% (w/w) polyamine.
24. The method of claim 1 , wherein the substrate comprises about 1 to about 4% (w/w) polyamine.
25. The method of claim 1 , wherein the substrate comprises about 1 to about 3% (w/w) polyamine.
26. The method of claim 1 , wherein the substrate comprises about 1 to about 2% (w/w) polyamine.
27. The method of claim 1 , wherein the phase invertible composition is produced by combining:
a substrate comprising about 1 to about 4% (w/w) branched polyethyleneimine, about 30% to about 50% albumin, and about 0.1% to about 0.3% chitosan, and
a crosslinking agent comprising a macromolecular crosslinking agent comprising a reaction product of about 3% to about 10% heat-treated glutaraldehyde and a glycosaminoglycan.
28. The method of claim 1 , wherein the phase invertible composition is produced by combining:
a substrate comprising about 1 to about 4% (w/w) branched polyethyleneimine, about 40% albumin, and about 0.16% chitosan, and
a crosslinking agent comprising a macromolecular crosslinking agent comprising a reaction product of about 4.4% to about 7.5% heat-treated glutaraldehyde and a glycosaminoglycan.