Biocompatible hydrogel treatments for retinal detachment
Provided herein are in vivo gelling ophthalmic pre-formulations forming a biocompatible retinal patch comprising at least one nucleophilic compound or monomer unit, at least one electrophilic compound or monomer unit, and optionally a therapeutic agent and/or viscosity enhancer. In some embodiments, the retinal patch at least partially adheres to the site of a retinal tear. Also provided herein are methods of treating retinal detachment by delivering an in vivo gelling ophthalmic pre-formulation to the site of a retinal tear in human eye, wherein the in vivo gelling ophthalmic pre-formulation forms a retinal patch.
1. A composition for the treatment of retinal detachment, comprising:
(a) multi-ARM nucleophilic polyol monomers having more than two nucleophilic arms, wherein each nucleophilic arm comprises a polyethylene glycol chain and terminates in a nucleophilic group selected from a hydroxyl, thiol, and amino;
(b) multi-ARM electrophilic polyol monomers having more than two electrophilic arms, wherein each electrophilic arm comprises a polyethylene glycol chain and terminates in an electrophilic group selected from an epoxide, maleimide, succinimidyl, and an alpha-beta unsaturated ester; and
(c) sodium hyaluronate;
wherein the viscosity of the composition is at least 4000 cP
wherein the composition gels when placed in the eye of a subject with retinal detachment.
2. The composition of claim 1 , wherein the composition further comprises a buffer providing a pH range of about 6.0 to about 8.5.
3. The composition of claim 1 , wherein the composition further comprises a therapeutic agent.
4. A composition for the treatment of retinal detachment, comprising:
(a) multi-ARM nucleophilic polyol monomers having more than two nucleophilic arms, wherein each nucleophilic arm comprises a polyethylene glycol chain and terminates in a nucleophilic group selected from a hydroxyl, thiol, and amino;
(b) multi-ARM electrophilic polyol monomers having more than two electrophilic arms, wherein each electrophilic arm comprises a polyethylene glycol chain and terminates in an electrophilic group selected from an epoxide, maleimide, succinimidyl, and an alpha-beta unsaturated ester; and
(c) sodium hyaluronate;
wherein the viscosity of the composition is at least 4000 cP,
wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from
wherein n is 1-200.
5. The composition of claim 1 , wherein the multi-ARM nucleophilic polyol monomers are selected from
wherein R is hexaglycerol or tripentaerythritol and wherein n is 1-200.
6. A composition for the treatment of retinal detachment, comprising:
(a) multi-ARM nucleophilic polyol monomers having more than two nucleophilic arms, wherein each nucleophilic arm comprises a polyethylene glycol chain and terminates in a nucleophilic group selected from a hydroxyl, thiol, and amino;
(b) multi-ARM electrophilic polyol monomers having more than two electrophilic arms, wherein each electrophilic arm comprises a polyethylene glycol chain and terminates in an electrophilic group selected from an epoxide, maleimide, succinimidyl, and an alpha-beta unsaturated ester; and
(c) sodium hyaluronate;
wherein the viscosity of the composition is at least 4000 cP,
wherein the electrophilic arms of the multi-ARM electrophilic polyol monomers are selected from
wherein m is 2 or 3 and n is 1-200.
7. The composition of claim 1 , wherein the multi-ARM electrophilic polyol monomers are selected from
wherein R is hexaglycerol or tripentaerythritol and n is 1-200.
8. The composition of claim 1 , wherein the composition comprises the following multi-ARM polyol monomers:
wherein R is hexaglycerol or tripentaerythritol, and
wherein n is such that the molecular weight of each of the polyol monomer is 20 kDa.
9. The composition of claim 8 , wherein the multi-ARM polyol monomer is in a hydrochloride salt form.
10. The composition of claim 1 , wherein the multi-ARM nucleophilic polyol monomers comprise
wherein R is hexaglycerol or tripentaerythritol, and wherein n is 1-200; and
the multi-ARM electrophilic polyol monomers comprise
wherein n is 1-200.
11. The composition of claim 10 , wherein the multi-ARM nucleophilic polyol monomer is in a hydrochloride salt form.
12. The composition of claim 1 , wherein the composition further comprises a dye.
13. A method of treating retinal detachment in a patient, comprising delivering a composition of claim 1 to a site of a retinal tear in a human eye, the composition comprising:
(a) multi-ARM nucleophilic polyol monomers having more than two nucleophilic arms, wherein each nucleophilic arm comprises a polyethyleneglycol chain and terminates in a nucleophilic group selected from a hydroxyl, thiol, and amino;
(b) multi-ARM electrophilic polyol monomers having more than two electrophilic arms, wherein each electrophilic arm comprises a polyethyleneglycol chain and terminates in an electrophilic group selected from epoxide, maleimide, succinimidyl, and an alpha-beta unsaturated ester; and
(c) sodium hyaluronate;
wherein the viscosity of the composition is at least 4000 cP;
and wherein the composition polymerizes and/or gels to form a biocompatible retinal patch when delivered to the site of the retinal tear to treat the retinal detachment in the patient.
14. The method of claim 13 , wherein the composition further comprises a buffer providing a pH range of about 6.0 to about 8.5.
15. The method of claim 13 , wherein the composition further comprises a therapeutic agent.
16. The method of claim 13 , wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from
wherein n is 1-200.
17. The method of claim 13 , wherein the multi-ARM nucleophilic polyol monomers are selected from
wherein R is hexaglycerol or tripentaerythritol, and
wherein n is 1-200.
18. The method of claim 13 , wherein the composition comprises the following multi-ARM polyol monomers:
wherein R is hexaglycerol or tripentaerythritol; and wherein n is 1 to 200.
19. The method of claim 18 , wherein the multi-ARM polyol monomer is in a hydrochloride salt form.
20. The method of claim 13 , wherein
the multi-ARM nucleophilic polyol monomers comprise
wherein R is hexaglycerol or tripentaerythritol, and wherein n is 1-200; and
the multi-ARM electrophilic polyol monomers comprise
wherein n is 1-200.
21. The method of claim 20 , wherein the multi-ARM nucleophilic polyol monomer is in a hydrochloride salt form.
22. The method of claim 13 , wherein the composition further comprises a dye.