Silicone Hydrogel Contact Lenses with Controlled and Extended Release of Latanopr

描述：该项目的目标是开发一种新型的可延长配戴时间的隐形眼镜，在配戴期间可控制和持续释放拉坦前列素来治疗青光眼。青光眼是世界上第二大致盲原因，全球青光眼病例总数估计超过7000万。通过非侵入性平台提供更有效和更方便的眼科治疗药物，尤其是青光眼药物，是非常有必要的。目前的治疗方案主要包括局部滴眼液，这会导致药物浓度和眼压(IOP)出现显著的高峰和低谷。拟议的工作旨在解决这些问题以及患者依从性差的问题，提高拉坦前列素的生物利用度，减少副作用，从而显著改善患者预后。新型硅胶水凝胶镜片将进行合理的设计和合成，在保持传统镜片性能(如光学清晰度、机械性能和氧气扩散率)的同时，显著控制拉坦前列素的释放和加载。的结构 这种透镜将通过改变组成和聚合条件来设计，通过聚合物透镜内的非共价相互作用为拉坦前列素产生大分子记忆，从而严格控制释放速度和装载量。将表征聚合物晶体的结构、机械和光学特性，以及在生理流动条件下的体外释放拉坦前列素，以匹配泪液流动速度和眼睛内的周转率。在体内，将评估工程隐形眼镜中拉坦前列素的释放，并与局部给药进行比较，测量眼压和眼内浓度随时间的变化。预计工程晶状体将导致恒定的拉坦前列素释放速率，并导致眼内药物浓度大致恒定，几乎没有峰和谷，在戴镜期间眼压持续下降。

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.