Silicone Hydrogel Contact Lenses with Controlled and Extended Release of Latanopr

产品说明：本项目的目的是开发一种新型长效接触透镜，在配戴期间可控制和持续释放拉坦前列素，以治疗青光眼。青光眼是世界上第二大致盲性疾病，全世界的病例总数估计超过7000万。对于经由非侵入性平台更有效和方便地递送眼部治疗剂，特别是青光眼药物，存在实质性需求。目前的治疗选择主要包括局部滴眼液，其导致药物浓度和眼内压（IOP）的显著峰值和谷值。拟议的工作旨在解决这些问题以及患者依从性差，增加拉坦前列素的生物利用度和减少副作用，从而显着改善患者的预后。 新型硅水凝胶镜片将被合理设计和合成，对拉坦前列素释放和负载具有显著控制，同时保持常规透镜性质，如光学透明度、机械性质和氧扩散率。的结构 该透镜将通过改变组成和聚合条件进行工程化，以通过聚合物透镜内的非共价相互作用产生拉坦前列素的大分子记忆，从而严格控制递送速率和装载量。将表征聚合物透镜的结构、机械、光学特性以及在与眼中泪液流速和转换相匹配的生理流动条件下的体外拉坦前列素释放。将评价拉坦前列素从工程角膜接触镜的体内释放，并与犬局部给药进行比较，测量IOP和眼内浓度随时间的变化。预期工程化镜片将导致拉坦前列素释放速率恒定，并导致眼睛中药物浓度大致恒定，几乎没有峰和谷，并且在透镜佩戴期间IOP恒定降低。

DESCRIPTION: The objective of this project is to develop a novel extended wear contact lens with controllable and sustained release of latanoprost for the duration of wear to treat glaucoma. Glaucoma is the second leading cause of blindness in the world with the total number of cases estimated at over 70 million worldwide. There is a substantial need for more efficacious and convenient delivery of ocular therapeutics, especially glaucoma medication, via non-invasive platforms. Current treatment options predominantly consist of topical eye drops, which lead to significant peaks and valleys in drug concentration and intraocular pressure (IOP). The proposed work aims to solve these problems as well as poor patient compliance with increased latanoprost bioavailability and decreased side effects leading to significantly better patient outcomes. Novel, silicone hydrogel lenses will be rationally designed and synthesized with significant control over latanoprost release and loading while maintaining conventional lens properties such as optical clarity, mechanical properties, and oxygen diffusivity. The structure of the lens will be engineered by varying composition and polymerization conditions to produce macromolecular memory for latanoprost via non-covalent interactions within the polymer lens, leading to strict control of delivery rate and loading. Polymer lens structural, mechanical, optica properties will be characterized as well as in vitro latanoprost release at physiological flow conditions that match tear flow rate and turnover in the eye. In vivo latanoprost release from engineered contact lenses will be evaluated and compared to topical administration in canines measuring IOP and ocular concentration versus time. It is expected that engineered lenses will lead to a constant rate of latanoprost release and lead to approximately constant concentrations of drug in the eye, with little to no peaks and valleys, and a constant decreased IOP for the duration of lens wear.