Hydrogel polymeric compositions and methods
Some aspects of this disclosure relate to a method of treating an ophthalmic disease affecting an eye of a patient comprising forming a covalently-crosslinked hydrogel for controlled release of a therapeutic agent.
1. A covalently cross-linked hydrogel for delivering a therapeutic agent to an eye comprising:
a polyamide copolymer comprising a first precursor covalently cross-linked to a second precursor, wherein the first precursor comprises a core having at least 80% by weight 4- to 8-arm polyethylene glycol having a molecular weight from about 12,000 Daltons to about 35,000 Daltons and wherein the second precursor comprises a core having at least 80% by weight 4- to 8-arm polyethylene glycol having a molecular weight of about 10,000 Daltons to about 35,000 Daltons or wherein the second precursor is trilysine; and
a therapeutic agent selected from a steroid, a non-steroidal anti-inflammatory drug, an intraocular pressure lowering drug, an antibiotic, and a pain reliever, wherein the therapeutic agent is in a particulate form and in direct contact with the polyamide copolymer and wherein the therapeutic agent is released from the hydrogel during a period of time in a range from 10 days to 50 days under exposure to a physiological solution, and
wherein the hydrogel has a weight increase of no more than about 50% upon exposure to a physiological solution for twenty-four hours relative to a weight of the hydrogel at the time of formation.
2. The covalently cross-linked hydrogel of claim 1 , wherein the therapeutic agent is a steroid.
3. The covalently cross-linked hydrogel of claim 1 , wherein the therapeutic agent is dexamethasone.
4. The covalently cross-linked hydrogel of claim 1 , wherein the hydrogel is adherent to a tissue at a site in or near an eye.
5. The covalently cross-linked hydrogel of claim 4 , wherein the adherence is to the sclera or other tissue near the sclera and promotes diffusion of the therapeutic agent through the tissue and into the back of the eye.
6. The covalently cross-linked hydrogel of claim 1 , wherein the therapeutic agent is entrapped in the polyamide copolymer.
7. The covalently cross-linked hydrogel of claim 1 , wherein the polyamide copolymer is water-degradable.
8. A synthetic, biocompatible polymeric hydrogel for delivering a therapeutic agent to an eye comprising:
a first water soluble synthetic precursor covalently crosslinked via amide linkages to a second water soluble synthetic precursor to form the hydrogel,
a small molecule therapeutic agent selected from a steroid, a non-steroidal anti-inflammatory drug, an intraocular pressure lowering drug, an antibiotic, and a pain reliever, wherein the therapeutic agent is in a particulate form free of encapsulating materials, with the therapeutic agent being in direct contact with the hydrogel and being releasable from the hydrogel during a period of time in a range from 10 days to 50 days under exposure to a physiological solution,
wherein any precursors that contribute to form the hydrogel are free of hydrophobic polymeric blocks and provide a molecular weight of 300-35,000 Daltons between crosslinks based on a 1:1 stoichiometric reaction between the first precursor and the second precursor,
wherein the hydrogel is internally covalently crosslinked and is low-swelling, as measurable by the hydrogel having a weight increasing no more than about 50% upon exposure to a physiological solution for twenty-four hours relative to a weight of the hydrogel at the time of formation, and wherein the hydrogel is water-degradable, as measurable by the hydrogel being dissolvable in vitro in an excess of water by degradation of the water-degradable group.
9. The hydrogel of claim 8 , wherein the therapeutic agent is a steroid.
10. The hydrogel of claim 8 , wherein the therapeutic agent is dexamethasone.
11. A method of treating an ophthalmic disease affecting an eye of a patient, the method comprising:
delivering a precursor composition to a site in or near an eye;
forming a covalently-crosslinked hydrogel in situ at the site from the precursor composition,
wherein the precursor composition comprises:
a first precursor comprising a core having at least 80% by weight 4- to 8-arm polyethylene glycol having a molecular weight from about 12,000 Daltons to about 35,000 Daltons;
a second precursor comprising a core having at least 80% by weight 4- to 8-arm polyethylene glycol having a molecular weight of about 10,000 Daltons to about 35,000 Daltons or trilysine; and
a therapeutic agent selected from a steroid, a non-steroidal anti-inflammatory drug, an intraocular pressure lowering drug, an antibiotic, and a pain reliever,
wherein the precursor composition has a viscosity from about 5 to about 10,000 centipoise and a gel time from about 2 minutes to about 10 minutes,
wherein the hydrogel comprises a polyamide copolymer.
12. The method of claim 11 , wherein the therapeutic agent is in a particulate form and in direct contact with the polyamide copolymer, and wherein the therapeutic agent is released from the hydrogel during a period of time in a range from 10 days to 50 days under exposure to a physiological solution.
13. The method of claim 11 , wherein the therapeutic agent is a steroid.
14. The method of claim 11 , wherein the therapeutic agent is dexamethasone.
15. The method of claim 11 , wherein the site comprises a topical, peri-ocular, intraocular, trans-scleral, between the conjunctival and scleral tissues, or an intra-vitreal site.