System for sutureless closure of scleral perforations and other ocular tissue discontinuities
The present disclosure describes, among other things, a thermo-responsive hydrogel comprising a PNIPAM copolymer having adhesive properties that are temperature dependent, as well as a device for administering the hydrogel, and methods for making and using the foregoing.
1. A temperature-responsive hydrogel comprising a poly(N-isopropylacrylamide) copolymer at a concentration of about 10 weight percent to about 60 weight percent in water, wherein the poly(N-isopropylacrylamide) copolymer (i) is a copolymer of poly(N-isopropylacrylamide) and a second polymer that is either a polymer of N-tert-butylacrylamide or butylacrylate, (ii) has a weight percent ratio of poly(N-isopropylacrylamide) to the second polymer of about 95:5 to about 70:30, and (iii) has a number average molecular weight of about 5,000 to about 5,000,000 daltons.
2. The hydrogel of claim 1 , wherein the poly(N-isopropylacrylamide) copolymer is a poly(N-isopropylacrylamide):N-tert-butylacrylamide copolymer.
3. The hydrogel of claim 1 , wherein the poly(N-isopropylacrylamide) copolymer is a poly(N-isopropylacrylamide):butylacrylate copolymer.
4. The hydrogel of claim 1 , wherein the weight percent ratio of poly(N-isopropylacrylamide) to the second polymer is selected from 99:1, 95:5, 90:10, 85:15, 80:20, 75:25, and 70:30.
5. The hydrogel of claim 1 , wherein the poly(N-isopropylacrylamide) copolymer has a number average molecular weight of about 10,000 to about 3,000,000 daltons.
6. The hydrogel of claim 1 , wherein the poly(N-isopropylacrylamide) copolymer has a number average molecular weight of about 20,000 to about 2,000,000 daltons.
7. The hydrogel of claim 1 , having a copolymer concentration in water selected from the group consisting of about 10 weight percent, 15 weight percent, 20 weight percent, 25 weight percent 30 weight percent, 35 weight percent, 40 weight percent, 45 weight percent, 50 weight percent, 55 weight percent, and 60 weight percent in water.
8. The hydrogel of claim 1 , having a lower critical solution temperature in a range of about 10° C. to about 35° C.
9. The hydrogel of claim 1 , wherein the poly(N-isopropylacrylamide) copolymer is a block copolymer.
10. The hydrogel of claim 1 , further comprising an excipient or additive.
11. The hydrogel of claim 1 in sterile form.
12. The hydrogel of claim 1 , having an adhesive strength of in a range between 10 mN to 10,000 mN when measured using an in vitro uniaxial adhesion test to scleral tissue at 37° C.
13. The hydrogel of claim 1 further comprising a bioactive agent.
14. An adhesive patch comprising the hydrogel of claim 1 .
15. The adhesive patch of claim 14 , comprising the hydrogel deposited on a polymeric substrate.
16. The adhesive patch of claim 15 , wherein the polymeric substrate is selected from the group consisting of parylene, poly-lactic acid, polyimide, and polydimethylsiloxane.
17. A method for reversibly sealing an ocular perforation, the method comprising applying a hydrogel of claim 1 to a tear in ocular tissue of a subject in an amount effective to seal the tear, wherein when exposed to a temperature above its critical solution temperature, the hydrogel becomes adhesive, and when exposed to a temperature below its critical solution temperature, the hydrogel becomes less adhesive.
18. The hydrogel of claim 1 , wherein the poly(N-isopropylacrylamide) copolymer has either formula I or formula II:
with x and y having values effective to provide copolymers with the number average molecular weight of about 5,000 to about 5,000,000 daltons.
19. The hydrogel of claim 1 wherein the poly(N-isopropylacrylamide) copolymer a number average molecular weight of about 30 kD to about 2,000 kD.
20. The hydrogel of claim 1 wherein the poly(N-isopropylacrylamide) copolymer a number average molecular weight of about 80 kD to about 2,000 kD.
21. The hydrogel of claim 1 wherein the poly(N-isopropylacrylamide) copolymer a number average molecular weight of about 100 kD to about 2,000 kD.
22. The hydrogel of claim 1 , having a copolymer concentration from about 15 weight percent to 60 weight percent in water.
23. The hydrogel of claim 1 , having a copolymer concentration from about 20 weight percent to 60 weight percent in water.
24. The hydrogel of claim 1 , having a copolymer concentration from about 25 weight percent to 60 weight percent in water.
25. The hydrogel of claim 1 , having a copolymer concentration from about 30 weight percent to 60 weight percent in water.
26. The hydrogel of claim 1 , having a copolymer concentration from about 25 weight percent to 35 weight percent in water.
27. The hydrogel of claim 1 , wherein the weight percent ratio of poly(N-isopropylacrylamide) to the second polymer is from 95:5 to 85:15.
28. The hydrogel of claim 1 , wherein the weight percent ratio of poly(N-isopropylacrylamide) to the second polymer is from 95:5 to 90:10.