Iodine-based particles

Abstract

Described herein are iodine-based particles which can be used as contrast agents for x-ray radiology. Also described herein are methods, software modules and hardware modules for imaging iodine-based particles.

What is claimed is: 
     
         1 . An iodine nanoparticle which is a reaction product of functionalized triiodobenzene, linking monomers, and biocompatible polymers;
 wherein said functionalized triiodobenzene, said linking monomers, and said biocompatible polymers are covalently cross-linked resulting in the structure of said nanoparticle being non-dendritic, non-uniform, and non-linear;   wherein said nanoparticle has a polydispersity index of about 0.5 or less;   wherein said nanoparticle has sufficient iodine density to be imaged by an imaging device following administration to a subject; and   wherein said nanoparticle provides for an extended blood half-life.   
     
     
         2 . The nanoparticle according to  claim 1  wherein said functionalized triiodobenzene is functionalized 1,3,5-triiodobenzene or functionalized 2,4,6-triiodobenzene. 
     
     
         3 . The nanoparticle according to  claim 1  wherein said functionalized triiodobenzene has the structure: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , and R 3  are each independently selected from a group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted amino, optionally substituted thiol, and optionally substituted phosphonate. 
     
     
         4 . The iodine nanoparticle according to  claim 1  wherein said functionalized triiodobenzene is 2,4,6-triiodophenol, 2-(2,4,6-triiodophenoxy)ethanol, 2-(2-bromoethoxy)1,3,5-triiodobenzene, (2,4,6-triiodophenoxy)acetamide, 2-(2,4,6-triiodophenoxy)ethanesulfonic acid, 3-hydroxy-2,4,6-triiodobenzoic acid, 3-amino-2,4,6-triiodobenzoic acid, methyl 2-(2,4,6-triiodophenoxy)butyrate, (2-(2,4,6-triiodophenoxy)-ethyl)trimethylammonium methanesulfonate, 5-amino-2,4,6-triiodoisophthalic acid, α-ethyl-3-hydroxy-2,4,6-triiodohydrocinnamic acid, iopanoic acid, 7-(3-amino-2,4,6-triiodophenyl)heptanoic acid, 7-(3-amino-2,4,6-triiodophenyl)heptanoic acid ethyl ester, 2-phenyl-2-(2,4,6-triiodophenoxy)acetic acid, (2-(3-hydroxy-2,4,6-triiodobenzyl)butyrylamino)acetic acid, N-(2-dimethylaminoethyl)-2-(3-hydroxy-2,4,6-triiodobenzyl)butyramide, (2-(3-hydroxy-2,4,6-triiodobenzyl)butyrylamino)acetic acid ethyl ester, 3-(acetylamino)-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoic acid, amidotrizoic acid, 3-acetamido-2,4,6-triiodobenzoic acid, bis(2-hydroxyethyl)-ammonium salt, 3-acetamido-2,4,6-triiodobenzoic acid, sodium salt dihydrate, 2-(3-hydroxy-2,4,6-triiodobenzyl)-N-(1-phenylethyl)butyramide, sodium diatrizoate hydrate, 3-(4-HO-Ph)-2-(2-(3-hydroxy-2,4,6-triiodobenzyl)-butyrylamino)propionic acid, 3-(acetylamino)-5-{[(2-hydroxyethyl)amino]carbonyl}-2,4,6-triiodobenzoic acid, 2-(3-hydroxy-2,4,6-triiodobenzyl)-N-(2-trifluoromethylphenyl)butyramide, meglumine diatrizoate, 3-acetamido-2,4,6-triiodobenzoic acid with 1-deoxy-1-(Me-amino)-glucit, 5-(N-2,3-dihydroxypropyl acetamido)-2,4,6-triiodo-N,N′-bis(2,3-dihydroxypropyl)isophthalamide, (2-(2-(3-hydroxy-2,4,6-triiodobenzyl)butyrylamino)thiazol-4-yl)acetic acid, 5-(N-2,3-dihydroxypropylacetamido)-2,4,6-triiodo-N,N′-bis(2,3-dihydroxypropyl)isophthalamide, 5-[N-(propylacetamido]-2,4,6-triiodo-N,N′-bis(propyl)isophthalamide, or any combination thereof. 
     
     
         5 . The iodine nanoparticle according to  claim 1  wherein said linking monomers are diaminoethane, diaminopropane, triamine, ethereal tetraamine, diisopropyl ethylamine, polyethyleneimine, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, dicarboxyethane, suberic acid, tricarboxylic acid, citrate, carboxycellulose, alginic acid, acrylic acid, carboxydextran, diethylenetriaminepentaacetic dianhydride, carbohydrazide, succinic dihydrazide, adipic acid dihydrazide, diglycidyl ether, 1,4-butadioldiglycidylether, polyethylene glycol diglycidyl, ethylene diamine, polyethylene amine, 1,1′-carbonyldiimidazole, or any combination thereof. 
     
     
         6 . The iodine nanoparticle according to  claim 1  wherein said biocompatible polymers are amine functionalized poly-N-vinylpyrrolidinone, polyvinyl alcohol, polysulfone, polyethylene terephthalate, polyether-urethanes, methoxy-polyethylene glycol, polyethyleneglycol-amine, polydimethylsiloxane, ethylene-co-vinylacetate, polymethylmethacrylate, polytetrafluoroethylene, polypropylene, polyethylene, alginic acid, polylysine, polyglycolide, polylactide, polylactide-co-glycolide, polycaprolactone, polybutylene succinate and its copolymers, poly-p-dioxanone, polycarbonate, aromatic copolyesters, polyamides, polyester-amides, polyurethane, polyphosphazenes, polyphosphoesters, collagen, albumin, gluten, chitosan, hyaluronate, cellulose, alginate, gelatin, starch or any combination thereof. 
     
     
         7 . The iodine nanoparticle according to  claim 1 , wherein said nanoparticle has a diameter from about 1 mm to about 100 mm. 
     
     
         8 . The iodine nanoparticle according to  claim 1 , wherein said nanoparticle has a diameter from about 0.25 μm to about 100 μm. 
     
     
         9 . The iodine nanoparticle according to  claim 1 , wherein said nanoparticle has a diameter from about 1 nm to about 500 nm. 
     
     
         10 . An encapsulated iodine particle comprising a hydrophobic core and an amphipathic encapsulating layer wherein said hydrophobic core consists of a hydrophobic iodine nanoparticle, a hydrophobic triiodobenzene monomer or a hydrophobic triiodobenzene dimer;
 wherein said iodine nanoparticle is a reaction product of functionalized triiodobenzene and linking monomers;   wherein said functionalized triiodobenzene and said linking monomers are covalently cross-linked resulting in the structure of said iodine nanoparticle being non-dendritic, non-uniform, and non-linear;   wherein said iodine nanoparticle has a polydispersity index of about 0.5 or less;   wherein said iodine nanoparticle has sufficient iodine density to be imaged by an imaging device following administration to a subject; and   wherein said iodine nanoparticle provides for an extended blood half-life.   
     
     
         11 . The encapsulated iodine particle according to  claim 10  wherein said functionalized triiodobenzene is functionalized 1,3,5-triiodobenzene or functionalized 2,4,6-triiodobenzene. 
     
     
         12 . The encapsulated iodine particle according to  claim 10  wherein said functionalized triiodobenzene has the structure: 
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , and R 3  are each independently selected from a group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted amino, optionally substituted thiol, and optionally substituted phosphonate. 
     
     
         13 . The encapsulated iodine particle according to  claim 10  wherein said functionalized triiodobenzene is 2,4,6-triiodophenol, 2-(2,4,6-triiodophenoxy)ethanol, 2-(2-bromoethoxy)1,3,5-triiodobenzene, (2,4,6-triiodophenoxy)acetamide, 2-(2,4,6-triiodophenoxy)ethanesulfonic acid, 3-hydroxy-2,4,6-triiodobenzoic acid, 3-amino-2,4,6-triiodobenzoic acid, methyl 2-(2,4,6-triiodophenoxy)butyrate, (2-(2,4,6-triiodophenoxy)-ethyl)trimethylammonium methanesulfonate, 5-amino-2,4,6-triiodoisophthalic acid, α-ethyl-3-hydroxy-2,4,6-triiodohydrocinnamic acid, iopanoic acid, 7-(3-amino-2,4,6-triiodophenyl)heptanoic acid, 7-(3-amino-2,4,6-triiodophenyl)heptanoic acid ethyl ester, 2-phenyl-2-(2,4,6-triiodophenoxy)acetic acid, (2-(3-hydroxy-2,4,6-triiodobenzyl)butyrylamino)acetic acid, N-(2-dimethylaminoethyl)-2-(3-hydroxy-2,4,6-triiodobenzyl)butyramide, (2-(3-hydroxy-2,4,6-triiodobenzyl)butyrylamino)acetic acid ethyl ester, 3-(acetylamino)-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoic acid, amidotrizoic acid, 3-acetamido-2,4,6-triiodobenzoic acid, bis(2-hydroxyethyl)-ammonium salt, 3-acetamido-2,4,6-triiodobenzoic acid, sodium salt dihydrate, 2-(3-hydroxy-2,4,6-triiodobenzyl)-N-(1-phenylethyl)butyramide, sodium diatrizoate hydrate, 3-(4-HO-Ph)-2-(2-(3-hydroxy-2,4,6-triiodobenzyl)-butyrylamino)propionic acid, 3-(acetylamino)-5-{[(2-hydroxyethyl)amino]carbonyl}-2,4,6-triiodobenzoic acid, 2-(3-hydroxy-2,4,6-triiodobenzyl)-N-(2-trifluoromethylphenyl)butyramide, meglumine diatrizoate, 3-acetamido-2,4,6-triiodobenzoic acid with 1-deoxy-1-(Me-amino)-glucit, 5-(N-2,3-dihydroxypropyl acetamido)-2,4,6-triiodo-N,N′-bis(2,3-dihydroxypropyl)isophthalamide, (2-(2-(3-hydroxy-2,4,6-triiodobenzyl)butyrylamino)thiazol-4-yl)acetic acid, 5-(N-2,3-dihydroxypropylacetamido)-2,4,6-triiodo-N,N′-bis(2,3-dihydroxypropyl)isophthalamide, 5-[N-(propylacetamido]-2,4,6-triiodo-N,N′-bis(propyl)isophthalamide, or any combination thereof. 
     
     
         14 . The encapsulated iodine particle according to  claim 10  wherein said linking monomers comprises diaminoethane, diaminopropane, triamine, ethereal tetraamine, diisopropyl ethylamine, polyethyleneimine, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, dicarboxyethane, suberic acid, tricarboxylic acid, citrate, carboxycellulose, alginic acid, acrylic acid, carboxydextran, diethylenetriaminepentaacetic dianhydride, carbohydrazide, succinic dihydrazide, adipic acid dihydrazide, diglycidyl ether, 1,4-butadioldiglycidylether, polyethylene glycol diglycidyl, ethylene diamine, polyethylene amine, 1,1′-carbonyldiimidazole, alkylamines, dodecylamine, oleylamine, octaoic hydrazide, or any combination thereof. 
     
     
         15 . The encapsulated iodine particle according to  claim 10  wherein said amphipathic polymer comprises polyethylene glycol, poly-D,L-lactic-coglycolic acid, polyethylene glycol-poly lactic acid, polyethylene glycol-polyepsilon-caprolactone, polysorbates, polyvinyl alcohol, polyvinyl pyrrolidone, dextran, chitosan, alginic acid, or carboxycellulose. 
     
     
         16 . The encapsulated iodine particle according to  claim 10 , wherein said particle has a diameter from about 1 mm to about 100 mm. 
     
     
         17 . The encapsulated iodine particle according to  claim 10 , wherein said particle has a diameter from about 0.25 μm to about 100 μm. 
     
     
         18 . The encapsulated iodine particle according to  claim 10 , wherein said particle has a diameter from about 1 nm to about 500 nm. 
     
     
         19 . A method of producing enhanced imaging by exposing the iodine nanoparticle according to  claim 1  to radiation. 
     
     
         20 . A method of producing enhanced imaging by exposing the encapsulated iodine particle according to  claim 10  to radiation.