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 polymeric composition, comprising an activated polyethylene glycol diacid derivative, and a covalent crosslinking agent; 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 5-10 inclusive; and w is 20 to 120 inclusive.
2. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons.
3. The polymeric composition of claim 1 , wherein m is 8.
4. The polymeric composition 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 polymeric composition of claim 1 , wherein the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine.
6. The polymeric composition 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 polymeric composition 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 polymeric composition 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 polymeric composition 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. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; and m is 8.
11. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; 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
12. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; and the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine.
13. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; and 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.
14. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; m is 8; and the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine.
15. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; m is 8; and 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 polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; m is 8; the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine; and 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.
17. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; 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; SSeb is
and the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine.
18. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; 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; SSeb is
and 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.
19. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; 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; SSeb is
the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine; and 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.
20. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; 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; SSeb is
the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine; and the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.5:1.
21. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; 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; SSeb is
the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine; and the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 0.75:1.
22. The polymeric composition of claim 1 , wherein the polyethyleneimine has a weight average molecular weight of about 2000 Daltons; 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; SSeb is
the polymeric composition comprises about 15 weight percent of the polyethylene glycol diacid derivative and the polyethyleneimine; and the molar ratio of activated esters on the polyethylene glycol diacid derivative to primary amines on the polyethyleneimine is about 1.15:1.