Reversible hydrogel systems and methods therefor
The present invention relates to reversible hydrogel systems for medical applications. Particularly, the hydrogel of the present invention is made up of copolymers that can be a hydrogel when in an oxidized state and can be a solution when in a reduced state. A solution of the copolymer can be oxidized to form a hydrogel; and the hydrogel can be reduced to form a solution of the copolymer. The solution can be dehydrated to produce the dry copolymer for storage. Furthermore, the present invention also relates to methods of making and using the reversible hydrogel systems.
1. A method of forming a replacement intraocular lens in situ in an eye comprising the steps of
a) introducing a reversible hydrogel system in solution into the capsular bag, wherein the reversible hydrogel system comprises a copolymer, wherein said copolymer is a hydrogel when in an oxidized state, and is a solution when in a reduced state, and wherein said copolymer is produced by polymerization of a monomer with a disulfide crosslinker, said monomer being selected from the group consisting of acrylamide, N-ornithine acrylamide, N-(2-hydroxypropyl)acrylamide, hydroxy-ethylacrylate, hydroxyethylmethacrylate, polyethyleneglycol acrylates, polyethyleneglycol methacrylates, N-vinyl pyrrolidone, N-phenylacrylamide, dimethylaminopropyl methacrylamide, acrylic acid, benzylmethacrylamide, and methylthioethylacrylamide; and
b) gelling the reversible hydrogel system.
2. The method of claim 1 , wherein the crosslinker is N, N′-bis(acryloyl)cystamine.
3. The method of claim 2 , wherein the oxidization occurs at a pH of about 6.5 to about 7.5.
4. The method of claim 2 , wherein the hydrogel is hydrophobic.
5. The method of claim 2 , wherein the hydrogel is hydrophilic.
6. The method of claim 2 , wherein the hydrogel is anionic.
7. The method of claim 2 , wherein the hydrogel is cationic.
8. The method of claim 2 , wherein the hydrogel can be reduced by the addition of a reducing agent.
9. The method of claim 8 , wherein the reducing agent is selected from the group consisting of dithiothreitol (DTT), 2-mercaptoethanol, dithioerythritol, cysteine, butanethiol, sodium borohydride, cyanoborohydride, mercaptoethylamine, ethylmaleimide, and tri(2-carboxyethyl)phosphine hydrochloride (TCEP.HCl).
10. The method of claim 2 , wherein the solution can be oxidized by atmospheric oxygen.
11. The method of claim 1 , wherein the reversible hydrogel system comprises a drug or particles.
12. The method of claim 11 , wherein the particles are proteins, polymers, or inorganic compounds.
13. The method of claim 11 , wherein the particles are nanoparticles.
14. The method of claim 13 , wherein the nanoparticles have sizes from about 4 nanometers (nm) to about 100 nm.
15. The method of claim 13 , wherein the nanoparticles do not scatter visible light.