Methods and polymer compositions for treating retinal detachment and other ocular disorders

Abstract

The invention provides methods and polymer compositions for treating retinal detachment and other ocular disorders, where the methods employ polymer compositions that can form a hydrogel in the eye of a subject. The hydrogel is formed by reaction of (i) a nucleo-functional polymer that is a biocompatible polymer containing a plurality of thio-functional groups —R 1 —SH wherein R 1 is an ester-containing linker, such as a thiolated poly(vinyl alcohol) polymer and (ii) an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group, such as a poly(ethylene glycol) polymer containing alpha-beta unsaturated ester groups.

1 - 127 . (canceled) 
     
     
         128 . A method of contacting retinal tissue in an eye of a subject with a polymer, the method comprising:
 a. administering to the vitreous cavity of the eye of the subject an effective amount of a nucleo-functional polymer and an electro-functional polymer; and   b. allowing the nucleo-functional polymer and the electro-functional polymer to react to form a hydrogel in the vitreous cavity;
 wherein the nucleo-functional polymer is a biocompatible polymer containing a plurality of thio-functional groups —R 1 —SH, wherein R 1  is an ester-containing linker, and the electro-functional polymer is a biocompatible polymer containing at least one thiol-reactive group. 
   
     
     
         129 . The method of  claim 128 , wherein the retinal tissue is contacted in the eye of a subject having a physical discontinuity in the retinal tissue, a tear in the retinal tissue, a break in the retinal tissue, or a hole in the retinal tissue. 
     
     
         130 . The method of  claim 128 , wherein the retinal tissue is contacted in a subject having undergone surgery for a macular hole, having undergone surgery to remove at least a portion of a epiretinal membrane, having undergone a vitrectomy for vitreomacular traction, having a rhegmatogenous retinal detachment, having tractional retinal detachment, or having serous retinal detachment. 
     
     
         131 . The method of  claim 128 , wherein the nucleo-functional polymer and the electro-functional polymer are administered separately as liquid aqueous pharmaceutical compositions or together as a single, liquid aqueous pharmaceutical composition to the vitreous cavity of the eye of the subject. 
     
     
         132 . The method of  claim 131 , wherein the separate liquid aqueous pharmaceutical compositions or single liquid aqueous pharmaceutical composition has a pH in the range of about 7.2 to about 7.6. 
     
     
         133 . The method of  claim 128 , wherein the hydrogel has a refractive index in the range of from about 1.2 to about 1.5. 
     
     
         134 . The method of  claim 128 , wherein the hydrogel has a transparency of at least 95% for light in the visible spectrum when measured through hydrogel having a thickness of 2 cm. 
     
     
         135 . The method of  claim 128 , wherein the hydrogel has a gelation time of less than about 10 minutes. 
     
     
         136 . The method of  claim 128 , wherein the hydrogel undergoes complete biodegradation from the eye of the subject within about 3 days to about 7 days, about 2 weeks to about 8 weeks, or about 4 months to about 6 months, or within 12 months or 24 months. 
     
     
         137 . The method of  claim 128 , wherein the hydrogel has a biodegradation half-life in the range of from about 1 week to about 3 weeks or from about 8 weeks to about 15 weeks when disposed within the vitreous cavity of an eye. 
     
     
         138 . The method of  claim 128 , wherein the hydrogel generates a pressure within the eye of less than 25 mmHg. 
     
     
         139 . The method of  claim 128 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 500 g/mol to about 1,000,000 g/mol; and
 wherein the electro-functional polymer has a weight-average molecular weight in the range of from about 500 g/mol to about 1,000,000 g/mol.   
     
     
         140 . The method of  claim 128 , wherein the mole ratio of (i) thio-functional groups —R 1 —SH to (ii) the at least one thiol-reactive group is in the range of 10:1 to 1:10, 5:1 to 1:1, or 2:1 to 1:1. 
     
     
         141 . The method of  claim 128 , wherein the retinal tissue is contacted in a subject having undergone a vitrectomy. 
     
     
         142 . An injectable, ocular formulation for forming a hydrogel in an eye of a subject, the formulation comprising:
 a. a nucleo-functional polymer that is a biocompatible polymer containing a plurality of thio-functional groups —R 1 —SH, wherein R 1  is an ester-containing linker;   b. an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group; and   c. a liquid pharmaceutically acceptable carrier for administration to the eye of the subject.   
     
     
         143 . The formulation of  claim 142 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 500 g/mol to about 1,000,000 g/mol; and
 wherein the electro-functional polymer has a weight-average molecular weight in the range of from about 500 g/mol to about 1,000,000 g/mol.   
     
     
         144 . The formulation of  claim 142 , wherein the mole ratio of (i) thio-functional groups —R 1 — SH to (ii) the at least one thiol-reactive group is in the range of 10:1 to 1:10, 5:1 to 1:1, or 2:1 to 1:1. 
     
     
         145 . The formulation of  claim 142 , wherein the formulation contains water, and the formulation has a pH in the range of about 7.1 to about 7.7.