Dendrimer compositions and their use in treatment of diseases of the eye

Abstract

The present invention provides compositions comprising PAMAM dendrimers conjugated with one or more biologically active agents, and their use systemically to target activated microglia/macrophages in retina/choroid and generally, inflammatory and/or angiogenic diseases of the eye.

1 - 13 . (canceled) 
     
     
         14 . A method for treating an inflammatory disease of the eye in a subject in need thereof, the method comprising:
 systemically administering to the subject a dendrimer composition in an amount effective to treat the inflammatory disease in the eye of the subject,   wherein the dendrimer composition comprises a hydroxyl-terminated dendrimer conjugated to one or more therapeutic agents.   
     
     
         15 . The method of  claim 14 , wherein the inflammatory disease of the eye is macular degeneration, macular edema, retinal vein occlusion, or geographic atrophy. 
     
     
         16 . The method of  claim 15 , wherein the macular degeneration is wet age-related macular degeneration. 
     
     
         17 . The method of  claim 15 , wherein the macular edema is diabetic macular edema. 
     
     
         18 . The method of  claim 15 , wherein the retinal vein occlusion is branch retinal vein occlusion. 
     
     
         19 . The method of  claim 14 , wherein the administering comprises intravenous or subcutaneous administration. 
     
     
         20 . The method of  claim 14 , wherein the one or more therapeutic agents are selected from proteins, oligonucleotides, and small molecules. 
     
     
         21 . The method of  claim 20 , wherein the one or more therapeutic agents are selected from enzymes, hormones, growth factors, antibodies, receptor antagonists or agonists, siRNA, and microRNA. 
     
     
         22 . The method of  claim 21 , wherein the one or more therapeutic agents are selected from anti-VEGF agents, COX-2 inhibitors, and antagonists of NF-κβ. 
     
     
         23 . The method of  claim 20 , wherein the one or more therapeutic agents are selected from N-acetyl-cysteine (NAC), triamcinolone acetonide, methyl prednisone, dexamethasone, minocycline, SN50, aflibercept, rapamycin, vitamin A, vitamin C, vitamin E, and beta-carotene. 
     
     
         24 . The method of  claim 14 , wherein the dendrimer composition is formulated in a liposome, a microcapsule, or a nanocapsule. 
     
     
         25 . The method of  claim 14 , wherein the hydroxyl-terminated dendrimer is a poly(amidoamine) (PAMAM) dendrimer. 
     
     
         26 . The method of  claim 14 , wherein the hydroxyl-terminated dendrimer is a generation 3, generation 4, generation 5, generation 6, generation 7, generation 8, generation 9, or generation 10 dendrimer. 
     
     
         27 . The method of  claim 14 , wherein the dendrimer composition is administered to the subject daily, weekly, monthly, or bimonthly. 
     
     
         28 . A method for detecting an inflammatory disease of the eye in a subject in need thereof, the method comprising:
 systemically administering to the subject a dendrimer composition in an amount effective to detect the inflammatory disease in the eye of the subject,   wherein the dendrimer composition comprises a hydroxyl-terminated dendrimer conjugated to one or more imaging agents.   
     
     
         29 . The method of  claim 28 , wherein the inflammatory disease of the eye is macular degeneration, macular edema, retinal vein occlusion, or geographic atrophy. 
     
     
         30 . The method of  claim 29 , wherein the inflammatory disease of the eye is wet age-related macular degeneration, diabetic macular edema, or branch retinal vein occlusion. 
     
     
         31 . The method of  claim 28 , wherein the administering comprises intravenous or subcutaneous administration. 
     
     
         32 . The method of  claim 28 , wherein the imaging agent is a fluorescent dye. 
     
     
         33 . The method of  claim 28 , wherein the hydroxyl-terminated dendrimer is a generation 3, generation 4, generation 5, generation 6, generation 7, generation 8, generation 9, or generation 10 PAMAM dendrimer.