Crosslinked polyalkyleneimine hydrogels with tunable degradation rates
One aspect of the present invention relates to methods of sealing a wound or tissue plane or filling a void space, or securing meshes, films or other devices within the body. In certain embodiments, the wound is an ophthalmic, pleural or dural wound, or a hernia repair mesh. Remarkably, disclosed herein is the discovery that the use of certain crosslinkers in combination with polyalkyleneimines at specific concentrations can result in hydrogels with tunable degradation properties.
1. A method of sealing a wound of a patient, comprising the steps of:
combining effective amounts of an activated polyethylene glycol diacid derivative and a covalent crosslinking agent to form a polymeric composition; and
applying said polymeric composition to a wound of a patient;
wherein the covalent crosslinking agent is polyethyleneimine having a weight average molecular weight of about 400 to about 2000 Daltons; the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is within a range of about 0.5:1 to about 1.5:1; and the activated polyethylene glycol diacid derivative is represented by formula I:
wherein, independently for each occurrence,
R is H; m is 5 to 10 inclusive; and w is 20 to 120 inclusive.
2. The method of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons.
3. The method of claim 1 , wherein m is 8.
4. The method of claim 1 , wherein the activated polyethylene glycol diacid derivative is PEG n -(SSeb) 2 ; wherein PEG is polyethylene glycol; n represents the number average molecular weight of the PEG; n is about 3350; and SSeb is
5. The method of claim 1 , wherein the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine.
6. The method of claim 1 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the crosslinking agent is in the range from about 0.75:1 to about 1.3:1.
7. The method of claim 1 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.5:1.
8. The method of claim 1 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.75:1.
9. The method of claim 1 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 1.15:1.
10. A method of augmenting soft tissue or filling a void of a patient, comprising the steps of:
combining effective amounts of an activated polyethylene glycol diacid derivative and a covalent crosslinking agent to form a polymeric composition; and
applying said polymeric composition to soft tissue or a void of a patient;
wherein the covalent crosslinking agent is polyethyleneimine having a weight average molecular weight of about 400 to about 2000 Daltons; the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is within a range of about 0.5:1 to about 1.5:1; and the activated polyethylene glycol diacid derivative is represented by formula I:
wherein, independently for each occurrence,
R is H; m is 5 to 10 inclusive; and w is 20 to 120 inclusive.
11. The method of claim 10 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons.
12. The method of claim 10 , wherein m is 8.
13. The method of claim 10 , wherein the activated polyethylene glycol diacid derivative is PEG n -(SSeb) 2 ; wherein PEG is polyethylene glycol; n represents the number average molecular weight of the PEG; n is about 3350; and SSeb is
14. The method of claim 10 , wherein the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine.
15. The method of claim 10 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the crosslinking agent is in the range from about 0.75:1 to about 1.3:1.
16. The method of claim 10 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.5:1.
17. The method of claim 10 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.75:1.
18. The method of claim 10 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 1.15:1.
19. A method of adhering tissues of a patient, comprising the steps of:
combining effective amounts of an activated polyethylene glycol diacid derivative and a covalent crosslinking agent to form a polymeric composition; and
applying said polymeric composition to a first tissue of a patient to form a modified tissue; and
contacting said modified tissue with a second tissue of the patient;
wherein the covalent crosslinking agent is polyethyleneimine having a weight average molecular weight of about 400 to about 2000 Daltons; the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is within a range of about 0.5:1 to about 1.5:1; and the activated polyethylene glycol diacid derivative is represented by formula I:
wherein, independently for each occurrence,
R is H; m is 5 to 10 inclusive; and w is 20 to 120 inclusive.
20. The method of claim 19 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons.
21. The method of claim 19 , wherein m is 8.
22. The method of claim 19 , wherein the activated polyethylene glycol diacid derivative is PEG n -(SSeb) 2 ; wherein PEG is polyethylene glycol; n represents the number average molecular weight of the PEG; n is about 3350; and SSeb is
23. The method of claim 19 , wherein the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine.
24. The method of claim 19 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the crosslinking agent is in the range from about 0.75:1 to about 1.3:1.
25. The method of claim 19 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.5:1.
26. The method of claim 19 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.75:1.
27. The method of claim 19 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 1.15:1.
28. A method of securing a prosthetic material to a tissue of a patient, comprising the steps of:
combining effective amounts of an activated polyethylene glycol diacid derivative and a covalent crosslinking agent to form a polymeric composition; and
applying said polymeric composition to the prosthetic material, thereby forming a modified prosthetic material; and
contacting the modified prosthetic material to the tissue of the patient, thereby securing the modified prosthetic material to the tissue of the patient;
wherein the covalent crosslinking agent is polyethyleneimine having a weight average molecular weight of about 400 to about 2000 Daltons; the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is within a range of about 0.5:1 to about 1.5:1; and the activated polyethylene glycol diacid derivative is represented by formula I:
wherein, independently for each occurrence,
R is H; m is 5 to 10 inclusive; and w is 20 to 120 inclusive.
29. The method of claim 28 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons.
30. The method of claim 28 , wherein m is 8.
31. The method of claim 28 , wherein the activated polyethylene glycol diacid derivative is PEG n -(SSeb) 2 ; wherein PEG is polyethylene glycol; n represents the number average molecular weight of the PEG; n is about 3350; and SSeb is
32. The method of claim 28 , wherein the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine.
33. The method of claim 28 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the crosslinking agent is in the range from about 0.75:1 to about 1.3:1.
34. The method of claim 28 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.5:1.
35. The method of claim 28 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.75:1.
36. The method of claim 28 , wherein the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 1.15:1.