Fabrication of Gold Nanoparticle-loaded Contact Lenses for Treating Ocular Cystinosis

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This grant supports research that advances the fabrication of contact lenses using nanoparticle-loaded hydrogels with a specific focus on treating ocular cystinosis. Incorporation of nanoparticles in hydrogels through polymerization is a scalable approach to controlling physical properties of the polymer, for example, elasticity, color, refractive index, conductivity and transport properties such as rates of drug release. This project involves incorporation of gold nanoparticles into contact lenses, which are made from either hydrogels or silicone hydrogels. Ocular cystinosis is a disease in which the cornea gets filled with crystals of cystine, which is the oxidized form of amino acid cysteine. The crystal formation eventually leads to many ocular complications including blindness. Typically, the disease is treated by hourly instillation of cysteamine eye drops. The drug reacts with cystine to dissolve the crystals. This grant is based on data that show that gold nanoparticles can bind significant amounts of cystine, thus, if a contact lens containing gold particles is placed on the eye, cystine diffuses from the cornea towards the contact lens, leading to crystal dissolution. The availability of nanostructured contact lenses loaded with gold nanoparticles advances treatment of ocular cystinosis and, thus, impacts the nation's health and welfare, benefiting society. The resulting 'GoldInLens' device could lead to drug-less cystinosis therapy. This research is inter-disciplinary and involves nanomanufacturing, materials science, transport behavior and pharmacy. The multi-disciplinary approach allows for broad training of the undergraduate and graduate students, and broaden participation of underrepresented groups.The gold particles are incorporated into the contact lens either by addition to the monomer mixture followed by polymerization, or by loading the polymerized lens with chloroauric acid and reduction by sodium citrate to form gold particles in situ. Fundamental studies explore the microstructure evolution during polymerization when nanoparticles are added to the monomer mixture, and the structure of gold aggregates that form in situ. Additionally, the impact of the particle incorporation on critical contact lens properties such as transparency, oxygen permeability and elastic modulus are investigated. Synergistic strategies are explored to maximize cystine capacity including developing contact lens materials with high capacity for cystine, and then increasing that capacity by incorporation of gold nanoparticles. The results from this research potentially have life-changing impact on patients with cystinosis by replacing hourly eye drop therapy with a contact lens worn for just a few hours each day. Additionally, the research unveils interesting fundamentals related to microstructure evolution during polymerization of nano-suspensions and structure of gold nano-aggregates than can form by using a small pore size hydrogel as a scaffold. The project advances several technological areas in nanomanufacturing, nanoscale devices, and particulate dispersions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.