Devices and methods for reducing cystine crystals in vivo

Abstract

According to some aspects, this application provides devices and methods for treating cystinosis in a patient. Removable intra-ocular devices and contact lenses containing cystine-sequestering materials effective for uptake of cystine from the eyes of a patient having cystinosis are provided. Methods of making the cystine-sequestering contact lenses are also provided.

1 . A removable intra-ocular device comprising:
 a cystine-sequestering material effective to uptake about 10 μg or more of cystine/day from the eye of a patient having cystinosis, wherein the cystine-sequestering material is selected from gold nanoparticles, metallic nanoparticles capable of binding cystine, methacrylic acids, hydroxyethyl methacrylate, thiolated compounds, monomers of these compounds, and combinations thereof.   
     
     
         2 . The removable intra-ocular device of  claim 1 , wherein the intra-ocular device is selected from the group consisting of: a contact lens, fornix inserts, puncta plugs, corneal rings, scleral lenses, sub-conjunctiva inserts, and intra cameral inserts into the aqueous humor. 
     
     
         3 . The removable intra-ocular device of  claim 1 , wherein the cystine-sequestering material is effective to uptake about 70-200 μg of cystine/day. 
     
     
         4 . (canceled) 
     
     
         5 . The removable intra-ocular device of  claim 1 , wherein the cystine-sequestering material comprises gold nanoparticles. 
     
     
         6 . The removable intra-ocular device of  claim 5 , wherein the gold nanoparticles have an average size of about 1 nm-200 nm. 
     
     
         7 .- 10 . (canceled) 
     
     
         11 . the intra-ocular device of  claim 1 , wherein the intra-ocular device is a contact lens comprising:
 a contact lens base material selected from hydrogel or silicon hydrogel, and a the cystine-sequestering material in the form of nanoparticles, wherein the nanoparticles are incorporated into the contact lens with the base material, coated on a surface of the contact lens, or both, wherein the cystine-sequestering material is present in an amount effective to uptake about 10 μg or more of cystine/day.   
     
     
         12 . The contact lens of  claim 11 , wherein the cystine-sequestering material is capable of uptake of about 70-200 μg of cystine/day. 
     
     
         13 .- 14 . (canceled) 
     
     
         15 . The contact lens of  claim 11 , wherein the cystine-sequestering material comprises gold nanoparticles. 
     
     
         16 . The contact lens of  claim 15 , wherein the gold nanoparticles have an average size of about 1 nm-200 nm. 
     
     
         17 .- 18 . (canceled) 
     
     
         19 . The contact lens of  claim 15 , wherein the loading of gold nanoparticles in the contact lens is about 0.2%-10% 
     
     
         20 . The contact lens of  claim 11 , wherein the lens base material is selected from hydroxyethyl methacrylate (HEMA), methacrylic acid, silicone-hydrogel, and combinations thereof. 
     
     
         21 .- 25 . (canceled) 
     
     
         26 . A method of making a disposable cystine-sequestering contact lens, the method comprising:
 providing a pre-formed contact lens having a contact lens matrix or providing a contact lens base material precursor capable of forming a contact lens matrix;   providing a cystine-sequestering material selected from the group consisting of: gold nanoparticles, metallic nanoparticles capable of binding cystine, methacrylic acids, hydroxyethyl methacrylate, thiolated compounds, monomers of these compounds, combinations thereof, and precursors thereof;   combining the pre-formed contact lens or the contact lens base material with the cystine-sequestering material or precursors thereof; and   forming the disposable cystine-sequestering contact lens having the cystine-sequestering material within the contact lens matrix in an amount effective to uptake cystine from the eye of a patient.   
     
     
         27 . The method of  claim 26 , wherein the pre-formed contact lens is a commercially available hydroxyethyl methacrylate lens (HEMA) or a silicone-hydrogel lens. 
     
     
         28 . The method of  claim 26 , wherein the cystine-sequestering material comprises gold nanoparticles, and wherein the gold nanoparticles are formed in the pre-formed contact lens in situ by soaking the pre-formed lens in gold chloride followed by soaking the lens in a mixture of citric acid and gold chloride, whereby gold particles form within pores of the pre-formed lens. 
     
     
         29 . The method of  claim 28 , wherein the gold chloride is chloroauric acid having a concentration of about 0.1-5% and wherein the citric acid has a concentration of 2-15 times the concentration of the gold chloride. 
     
     
         30 . The method of  claim 29 , wherein the ratio of citric acid to chloroauric acid is from about 1 to 15. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 26 , wherein the contact lens base material precursor is a hydroxyethyl methacrylate (HEMA) monomer and wherein the method further comprises mixing the HEMA monomer with an aqueous phase comprising gold nanoparticles and a crosslinker, placing the mixture in a mold, and polymerizing the HEMA monomer to form a HEMA polymer matrix such that the gold nanoparticles are embedded in the HEMA polymer matrix. 
     
     
         33 . The method of  claim 32 , wherein the gold nanoparticles have a concentration of about 1-5%. 
     
     
         34 . The method of  claim 32 , wherein the crosslinker is ethylene glycol dimethacrylate (EGDMA). 
     
     
         35 . (canceled) 
     
     
         36 . A method of treating cystinosis comprising:
 providing, for a patient in need of treatment for cystinosis, a disposable contact lens of  claim 11  with instructions to wear the contact lens in the eye of the patient for at least 8 hours/day, wherein the contact lens is effective to remove about 70 μg, or more, of cystine per day from the eye of the patient.