Ocular iontophoretic device and method for inhibiting vascular endothelial growth factor (VEGF) using the same

Abstract

An ocular iontophoretic device for delivering an aptamer to an affected area of a living being's eye for inhibiting VEGF function therein, the device comprising an active electrode assembly associated with a matrix and/or reservoir, wherein the matrix and/or reservoir includes an aptamer capable of inhibiting VEGF function. A method for treating an affected area of a living being's eye, comprising the steps of: associating an aptamer with an ocular iontophoretic device; positioning at least a portion of an ocular iontophoretic device on the eye of the living being; and iontophoretically delivering the aptamer to an affected area of the living being's eye.

What is claimed is:  
     
         1 . An ocular iontophoretic device for delivering an aptamer to an affected area of a living being's eye for inhibiting VEGF function therein, the device comprising: 
 an active electrode assembly associated with a matrix, wherein the matrix includes an aptamer capable of inhibiting VEGF function.    
     
     
         2 . The ocular iontophoretic device according to  claim 1 , wherein the matrix includes an aptamer capable of inhibiting at least one VEGF selected from the group consisting of VEGF-121, VEGF-165, VEGF-189, and VEGF-206.  
     
     
         3 . The ocular iontophoretic device according to  claim 1 , wherein the matrix includes an aptamer capable of inhibiting VEGF-165.  
     
     
         4 . The ocular iontophoretic device according to  claim 1 , wherein the matrix further comprises a PEGylating agent which slows enzymatic tissue digestion of the aptamer upon delivery of the same to the affected area of the living being's eye.  
     
     
         5 . The ocular iontophoretic device according to  claim 4 , wherein the PEGylating agent includes a moiety selected from the group consisting of isocyanates, amino groups, and mixtures thereof.  
     
     
         6 . The ocular iontophoretic device according to  claim 1 , wherein the aptamer is present in a concentration between approximately 0.1 mg and approximately 10 mg of aptamer per ml of water.  
     
     
         7 . The ocular iontophoretic device according to  claim 6 , wherein the water is buffered to a pH ranging between approximately 6.5 and approximately 8.5.  
     
     
         8 . The ocular iontophoretic device according to  claim 1 , wherein the affected area of the eye is selected from at least one of the group consisting of the vitreous humor, retina, choroid, circulation of the retina, circulation of the choroid, and sclera.  
     
     
         9 . The ocular iontophoretic device according to  claim 1 , further comprising: 
 a counter electrode assembly, wherein the counter electrode assembly is configured for completing an electrical circuit between the active electrode assembly and an energy source; and    an energy source for generating an electrical potential difference.    
     
     
         10 . An ocular iontophoretic device for delivering an aptamer to an affected area of a living being's eye for inhibiting VEGF function therein, the device comprising: 
 a matrix, wherein the matrix is capable of temporarily retaining a solution having an aptamer;    an active electrode assembly associated with the matrix, wherein the active electrode assembly is configured for iontophorectically delivering the aptamer to the affected area of the living being's eye;    a counter electrode assembly, wherein the counter electrode assembly is configured for completing an electrical circuit between the active electrode assembly and an energy source; and    an energy source for generating an electrical potential difference.    
     
     
         11 . An ocular iontophoretic device for delivering an aptamer to an affected area of a living being's eye for inhibiting VEGF function therein, the device comprising: 
 a reservoir, wherein the reservoir includes an aptamer capable of inhibiting VEGF function;    a matrix, wherein the matrix is capable of temporarily retaining a solution having an aptamer;    an active electrode assembly associated with the matrix, wherein the active electrode assembly is configured for iontophorectically delivering the aptamer to the affected area of the living being's eye;    a counter electrode assembly, wherein the counter electrode assembly is configured for completing an electrical circuit between the active electrode assembly and an energy source; and    an energy source for generating an electrical potential difference.    
     
     
         12 . The ocular iontophoretic device according to  claim 11 , wherein the reservoir includes an aptamer capable of inhibiting at least one VEGF selected from the group consisting of VEGF-121, VEGF-165, VEGF-189, and VEGF-206.  
     
     
         13 . The ocular iontophoretic device according to  claim 11 , wherein the reservoir includes an aptamer capable of inhibiting VEGF-165.  
     
     
         14 . The ocular iontophoretic device according to  claim 11 , wherein the reservoir further comprises a PEGylating agent which slows enzymatic tissue digestion of the aptamer upon delivery of the same to the affected area of the living being's eye.  
     
     
         15 . The ocular iontophoretic device according to  claim 14 , wherein the PEGylating agent includes a moiety selected from the group consisting of isocyanates, amino groups, and mixtures thereof.  
     
     
         16 . The ocular iontophoretic device according to  claim 11 , wherein the aptamer is present in a concentration between approximately 0.1 mg and approximately 10 mg of aptamer per ml of water.  
     
     
         17 . The ocular iontophoretic device according to  claim 16 , wherein the water is buffered to a pH ranging between approximately 6.5 and approximately 8.5.  
     
     
         18 . The ocular iontophoretic device according to  claim 11 , wherein the affected area of the eye is selected from at least one of the group consisting of the vitreous humor, retina, choroids, circulation of the retina, circulation of the choroid, and sclera.  
     
     
         19 . A method for treating an affected area of a living being's eye, comprising the steps of: 
 associating an aptamer with an ocular iontophoretic device;    positioning at least a portion of the ocular iontophoretic device on the eye of a living being; and    iontophoretically delivering the aptamer to an affected area of the living being's eye.    
     
     
         20 . The method according to  claim 19 , wherein the step of associating the aptamer includes the step of associating an aptamer capable of inhibiting VEGF function.  
     
     
         21 . The method according to  claim 19 , wherein the step of associating the aptamer includes the step of associating an aptamer capable of inhibiting at least one VEGF selected from the group consisting of VEGF-121, VEGF-165, VEGF-189, and VEGF-206.  
     
     
         22 . The method according to  claim 19 , wherein the step of associating the aptamer includes the step of associating an aptamer capable of inhibiting VEGF-165.  
     
     
         23 . The method according to  claim 19 , further comprising the step of associating a PEGylating agent with the aptamer.  
     
     
         24 . The method according to  claim 23 , wherein the step of associating a PEGylating agent includes the step of associating a PEGylating agent comprising a moiety selected from the group consisting of isocyanates, amino groups, and mixtures thereof.  
     
     
         25 . The method according to  claim 19 , wherein the step of associating an aptamer includes the step of associating an aptamer present in a concentration between approximately 0.1 mg and approximately 10 mg of aptamer per ml of water, wherein the water is buffered to a pH ranging between approximately 6.5 and approximately 8.5.  
     
     
         26 . The method according to  claim 19 , wherein the step of iontophoretically delivering the aptamer, includes the step of iontophoretically delivering the aptamer to at least one of the group consisting of the vitreous humor, retina, choroid, circulation of the retina, circulation of the choroid, and sclera.  
     
     
         27 . The method according to  claim 19 , wherein the step of iontophoretically delivering the aptamer, includes the step of iontophoretically loading a sclera of the living being's eye with the aptamer for prolonged delivery into back regions of the living being's eye.  
     
     
         28 . The method according to  claim 19 , wherein the step of iontophoretically delivering the aptamer, includes the step of iontophoretically delivering the aptamer at a current between approximately 0.1 mA and approximately 4 mA for a period of between approximately 1 and approximately 60 minutes.  
     
     
         29 . The method according to  claim 19 , wherein the step of iontophoretically delivering the aptamer, includes the step of delivering the aptamer using negative polarity electrical current.  
     
     
         30 . The method according to  claim 19 , wherein the step of positioning at least a portion of the ocular iontophoretic device on the eye of a living being includes the step of applying at least a portion of the ocular iontophoretic device to a conjunctival surface in a region of a pars planum.  
     
     
         31 . A method for inhibiting VEGF function within an affected area of a living being's eye, comprising the steps of: 
 associating an aptamer with a matrix of an ocular iontophoretic device;    associating the ocular iontophoretic device having an active electrode assembly with the eye of the living being;    iontophorectically delivering an effective amount of the aptamer to an affected area of the living being's eye having an amount of VEGF;    binding the effective amount of aptamer to the amount of VEGF; and    inhibiting function of the amount of VEGF.    
     
     
         32 . The method according to  claim 31 , wherein the step of associating the aptamer includes the step of associating an aptamer capable of inhibiting VEGF function.  
     
     
         33 . The method according to  claim 31 , wherein the step of associating the aptamer includes the step of associating an aptamer capable of inhibiting at least one VEGF selected from the group consisting of VEGF-121, VEGF-165, VEGF-189, and VEGF-206.  
     
     
         34 . The method according to  claim 31 , wherein the step of associating the aptamer includes the step of associating an aptamer capable of inhibiting VEGF-165.  
     
     
         35 . The method according to  claim 31 , further comprising the step of associating a PEGylating agent with the aptamer.  
     
     
         36 . The method according to  claim 35 , wherein the step of associating a PEGylating agent includes the step of associating a PEGylating agent comprising a moiety selected from the group consisting of isocyanates, amino groups, and mixtures thereof.  
     
     
         37 . The method according to  claim 31 , wherein the step of associating an aptamer includes the step of associating an aptamer present in a concentration between approximately 0.1 mg and approximately 10 mg of aptamer per ml of water, wherein the water is buffered to a pH ranging between approximately 6.5 and approximately 8.5.  
     
     
         38 . The method according to  claim 31 , wherein the step of iontophoretically delivering the aptamer, includes the step of iontophoretically delivering the aptamer to at least one of the group consisting of the vitreous humor, retina, choroid, circulation of the retina, circulation of the choroid, and sclera.  
     
     
         39 . The method according to  claim 31 , wherein the step of iontophoretically delivering the aptamer, includes the step of iontophoretically loading a sclera of the living being's eye with an effective amount of the aptamer for prolonged delivery into back regions of the living being's eye.  
     
     
         40 . The method according to  claim 31 , wherein the step of iontophoretically delivering the aptamer, includes the step of iontophoretically delivering an effective amount of the aptamer at a current between approximately 0.1 mA and approximately 4 mA for a period of between approximately 1 and approximately 60 minutes.  
     
     
         41 . The method according to  claim 31 , wherein the step of iontophoretically delivering the aptamer, includes the step of delivering the aptamer using negative polarity electrical current.  
     
     
         42 . The method according to  claim 31 , wherein the step of associating the ocular iontophoretic device having an active electrode assembly with the eye of the living being includes the step of applying at least a portion of the ocular iontophoretic device to a conjunctival surface in a region of a pars planum.