Formulations for the Suprachoroidal Space of an Eye and Methods

Abstract

Provided herein are fluid formulations for administration to a suprachoroidal space of an eye of a patient. The fluid formulations may include a pharmaceutical agent, a binding molecule, or a combination thereof. The pharmaceutical agent and the binding molecule may be bonded to each other covalently, non-covalently, or a combination thereof. The pharmaceutical agent may be configured to bond to an ocular tissue. The binding molecule may be configured to bond to an ocular tissue. Methods of administering the fluid formulations, methods of expanding a suprachoroidal space, and methods of reducing the minimum force to separate the sclera and choroid are provided.

We claim: 
     
         1 . A method of expanding a suprachoroidal space of an eye, the method comprising:
 inserting a microneedle into the eye at an insertion site; and then   infusing through the microneedle into the suprachoroidal space a first liquid formulation having a volume and a viscosity sufficient to expand at least a portion of the suprachoroidal space to a thickness of about 500 μm to about 3.0 mm for at least two hours after the infusing.   
     
     
         2 . The method of  claim 1 , wherein the first liquid formulation is configured to solidify in the suprachoroidal space. 
     
     
         3 . The method of  claim 1 , wherein the first liquid formulation is configured to form a crosslinked hydrogel in the suprachoroidal space. 
     
     
         4 . The method of  claim 1 , wherein the first liquid formulation comprises an additive at a concentration sufficient to draw a portion of one or more ocular fluids into the suprachoroidal space. 
     
     
         5 . The method of  claim 1 , wherein the thickness is maintained for at least eight hours after the infusing. 
     
     
         6 . The method of  claim 1 , wherein the thickness is maintained for at least twenty-four hours after the infusing. 
     
     
         7 . The method of  claim 1 , wherein the thickness is maintained for at least one month after the infusing. 
     
     
         8 . The method of  claim 1 , wherein the viscosity of the first liquid formulation is sufficient to expand the suprachoroidal space to a thickness of about 750 μm to about 2.8 mm. 
     
     
         9 . The method of  claim 1 , wherein the viscosity of the first liquid formulation is sufficient to expand the suprachoroidal space to a thickness of about 1 mm to about 2 mm. 
     
     
         10 . The method of  claim 1 , wherein the viscosity of the first liquid formulation is at least 1×10 3  cP. 
     
     
         11 . The method of  claim 1 , further comprising infusing a volume of a second liquid formulation prior to infusing the first liquid formulation, wherein the volume of the second liquid formulation is sufficient to reduce by at least 25% the minimum force to separate the sclera and choroid bounding the suprachoroidal space. 
     
     
         12 . The method of  claim 11 , wherein the volume of the second liquid formulation is sufficient to reduce the minimum force to separate the sclera and choroid by about 30% to about 80%. 
     
     
         13 . The method of  claim 11 , wherein the viscosity of the second liquid formulation is greater than 1 cP. 
     
     
         14 . The method of  claim 11 , wherein the second liquid formulation comprises water and a polysaccharide, wherein the polysaccharide is present at a concentration of about 1% to about 40% by weight, based on the weight of the second liquid formulation. 
     
     
         15 . The method of  claim 14 , wherein the polysaccharide comprises carboxymethylcellulose, dextran, hyaluronic acid, or a combination thereof. 
     
     
         16 . The method of  claim 11 , wherein the second liquid formulation comprises water and a polysaccharide, wherein the polysaccharide is present at a concentration of about 1% to about 10% by weight, based on the weight of the second liquid formulation. 
     
     
         17 . A method of expanding a suprachoroidal space of an eye, the method comprising:
 inserting a microneedle into the eye at an insertion site; and then   infusing through the microneedle into the suprachoroidal space a first liquid formulation having a volume and a viscosity sufficient to expand at least a portion of the suprachoroidal space to a thickness of about 500 μm to about 3.0 mm for a period exceeding 24 hours after the infusing;   wherein the first liquid formulation is configured to solidify, form a crosslinked hydrogel, or a combination thereof in the suprachoroidal space.   
     
     
         18 . The method of  claim 17 , wherein the viscosity of the first liquid formulation is sufficient to expand the suprachoroidal space to a thickness of about 750 μm to about 2.8 mm. 
     
     
         19 . The method of  claim 17 , wherein the viscosity of the first liquid formulation is sufficient to expand the suprachoroidal space to a thickness of about 1 mm to about 2 mm. 
     
     
         20 . The method of  claim 17 , wherein the viscosity of the first liquid formulation is at least 1×10 3  cP.