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

该基金支持使用纳米颗粒负载水凝胶推进隐形眼镜制造的研究，重点是治疗眼胱氨酸病。通过聚合将纳米颗粒掺入水凝胶是一种可扩展的方法，可以控制聚合物的物理特性，例如弹性、颜色、折射率、电导率和药物释放率等传输特性。这个项目包括将金纳米颗粒掺入隐形眼镜中，这种隐形眼镜由水凝胶或硅水凝胶制成。眼胱氨酸病是一种角膜充满胱氨酸晶体的疾病，胱氨酸是氨基酸半胱氨酸的氧化形式。晶体的形成最终会导致许多眼部并发症，包括失明。通常，这种疾病的治疗方法是每小时滴注半胱胺滴眼液。这种药物与胱氨酸反应溶解晶体。这项拨款的依据是，有数据显示，金纳米颗粒可以结合大量的胱氨酸，因此，如果将含有金颗粒的隐形眼镜戴在眼睛上，胱氨酸就会从角膜向隐形眼镜扩散，导致晶体溶解。含有金纳米颗粒的纳米结构隐形眼镜的可用性促进了眼胱氨酸病的治疗，从而影响了国家的健康和福利，造福了社会。由此产生的“GoldInLens”装置可能会导致无药物胱氨酸病的治疗。这项研究是跨学科的，涉及纳米制造、材料科学、运输行为和药学。多学科的方法允许对本科生和研究生进行广泛的培训，并扩大代表性不足群体的参与。将金颗粒加入到单体混合物中然后进行聚合，或者将聚合后的镜片装入氯金酸并通过柠檬酸钠还原以原位形成金颗粒。基础研究探讨了聚合过程中纳米粒子加入到单体混合物中的微观结构演变，以及原位形成的金聚集体的结构。此外，还研究了颗粒掺入对隐形眼镜透明度、透氧性和弹性模量等关键性能的影响。为了最大限度地提高胱氨酸容量，研究人员探索了协同策略，包括开发具有高胱氨酸容量的隐形眼镜材料，然后通过加入金纳米颗粒来增加胱氨酸容量。这项研究的结果可能会改变胱氨酸病患者的生活，用每天戴几小时的隐形眼镜代替每小时滴眼液治疗。此外，该研究揭示了纳米悬浮液聚合过程中微观结构演变的有趣基础，以及使用小孔径水凝胶作为支架形成的金纳米聚集体的结构。该项目推进了纳米制造、纳米级器件和颗粒分散的几个技术领域。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.