Methods for the formation of hydrogels using thiosulfonate compositions and uses thereof
The present invention provides both crosslinked polymer compositions capable of forming hydrogels upon exposure to an aqueous environment and thiosulfonate hydrogel-forming components. The thiosulfonate hydrogel-forming components of the invention are preferably multi-arm thiosulfonate polymer derivatives that form a crosslinked polymer composition when exposed to a base without requiring the presence of a second cross-linking reagent, redox catalyst, or radiation. Methods for forming hydrogel compositions, as well as methods for using the hydrogels, are also provided.
1. A compound having the formula:
wherein:
POLY is a water-soluble polymer;
(n) is 3 to about 25;
X is a linking group;
Y is moiety derived from a molecule having at least three nucleophilic groups, and R is an organic radical;
POLY′ is water-soluble polymer (either the same or different than POLY);
Z is a functional group having low reactivity with thiosulfonate, sulfhydryl, and disfulde linkages; and
(m) is a positive integer.
2. The compound of claim 1 , wherein both POLY and POLY′ are the water-soluble poly(ethylene glycol)s.
3. The compound of claim 1 , wherein (n) is 3 to 10.
4. The compound of claim 3 , wherein (n) is 3.
5. The compound of claim 3 , wherein (n) is 4.
6. The compound of claim 3 , wherein (n) is 5.
7. The compound of claim 6 , wherein (n) is 6.
8. The compound of claim 1 , wherein the organic radical is alkyl or aryl.
9. The compound of claim 1 , wherein the organic radical is methyl.
10. The compound of claim 1 , wherein the organic radical is phenyl.
11. The compound of claim 2 , wherein each of the poly(ethylene glycol)s has a molecular weight of from 200 Da to about 20,000 Daltons.
12. The compound of claim 11 , wherein each of the poly(ethylene glycol)s has a molecular weight of from 500 Da to about 15,000 Daltons.
13. The compound of claim 11 , wherein each of the poly(ethylene glycol)s has a molecular weight of from 600 Da to about 6,000 Daltons.
14. The compound of claim 1 , wherein the molecule having at least three nucleophilic groups is selected from the group consisting of glycerol, oligoglycerols, pentaerythritol, carbohydrates, and cyclodextrin.
15. The compound of claim 1 , wherein the molecule having at least three nucleophilic groups is glycerol.
16. The compound of claim 1 , wherein the molecule having at least three nucleophilic groups is an oligoglycerol.
17. The compound of claim 1 , wherein the molecule having at least three nucleophilic groups is
18. The compound of claim 1 , wherein the molecule having at least three nucleophilic groups is pentaerythritol.
19. The compound of claim 1 , wherein the molecule having at least three nucleophilic groups is 1,2,3-propane-triamine.
20. The compound of claim 1 , wherein (m) is selected from the group consisting of 1, 2, 3, 5 and 10.