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. An in vivo gelling pre-formulation 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 polyethyleneglycol chain and terminates in a nucleophilic amino group; wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from
and wherein n is 1-200;
(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 succinimidyl group; wherein the electrophilic arms of the multi-ARM electrophilic polyol monomers are selected from
wherein m is 2 or 3; and
wherein n is 1-200; and
(c) a viscosity enhancer selected from carboxymethylcellulose sodium, ethylcellulose, sodium alginate and mixtures thereof;
wherein the viscosity of the in vivo gelling pre-formulation is between about 5 cP and 4000 cP;
and
wherein the in vivo gelling pre-formulation polymerizes and/or gels at a target site of an eye to form a biocompatible retinal patch.
2. The in vivo gelling pre-formulation of claim 1 , wherein the pre-formulation further comprises a buffer providing a pH range of about 6.0 to about 8.5.
3. The in vivo gelling pre-formulation of claim 1 , wherein the pre-formulation further comprises a therapeutic agent.
4. The in vivo gelling pre-formulation 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.
5. The in vivo gelling pre-formulation of claim 1 , wherein the multi-ARM electrophilic polyol monomers are selected from
wherein R is hexaglycerol or tripentaerythritol; and
wherein n is 1-200.
6. The in vivo gelling pre-formulation of claim 1 , wherein the pre-formulation is prepared from 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.
7. A method of treating retinal detachment, comprising delivering an in vivo gelling pre-formulation to a site of a retinal tear in a human eye, the in vivo gelling pre-formulation 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 amino group; wherein the nucleophilic arms of the multi-ARM nucleophilic polyol monomers are selected from
and wherein n is 1-200;
(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 succinimidyl group; wherein the electrophilic arms of the multi-ARM electrophilic polyol monomers are selected from
wherein m is 2 or 3; and
wherein n is 1-200; and
(c) a viscosity enhancer selected from carboxymethylcellulose sodium, ethylcellulose, sodium alginate, and mixtures thereof;
wherein the viscosity of the in vivo gelling pre-formulation is between about 5 cP and 4000 cP;
and
wherein the in vivo gelling pre-formulation polymerizes and/or gels at a target site of an eye to form a biocompatible retinal patch.
8. The method of claim 7 , wherein the pre-formulation further comprises a buffer providing a pH range of about 6.0 to about 8.5.
9. The method of claim 7 , wherein the pre-formulation further comprises a therapeutic agent.
10. The method of claim 7 , wherein the multi-ARM nucleophilic polyol monomers are selected from
wherein R is hexaglycerol or tripentaerythritol; and
wherein n is 1-200.
11. The method of claim 7 , wherein the pre-formulation is prepared from the following multi-ARM polyol monomers:
wherein R is hexaglycerol or tripentaerythritol; and
wherein n is 1 to 200.
12. The in vivo gelling pre-formulation of claim 1 , wherein the viscosity enhancer is ethylcellulose.
13. The in vivo gelling pre-formulation of claim 1 , wherein the viscosity enhancer is selected from sodium alginate, carboxymethylcellulose sodium and mixtures thereof.
14. The method of claim 7 , wherein the viscosity enhancer is ethylcellulose.
15. The method of claim 7 , wherein the viscosity enhancer is selected from sodium alginate, carboxymethylcellulose sodium and mixtures thereof.