Drug delivery platform for ocular allergy therapy

项目总结 据估计，全球有1.65亿隐形眼镜佩戴者，其中许多人患有过敏症，但面临着挑战 因为眼药水的使用通常与配戴镜片不相容。据估计有三分之一的人 戴隐形眼镜的人眼睛发痒；其中大多数人对过敏干扰他们的眼睛感到沮丧 正常佩戴，经常依赖过敏性眼药水来控制症状。第一次批准 解决这一需求的药物隐形眼镜直到最近(2021年)才出现，当时强生的 Acuvue Theravision用酮替芬药物洗脱日用一次性水凝胶镜片获得上市许可 在日本。我们建议开发用于过敏药物的下一代药物递送隐形眼镜(DDCL)平台 使用边界电荷修饰剂来延长和控制药物释放。这项工作将在我们以前工作的基础上进行 在外地取得的成就--既能使用最有效的药物，又能呼吸最好的药物 隐形眼镜。强生的新产品需要在这两个方面做出妥协，才能在几个小时内完成 释放期限。许多商用隐形眼镜既可延长佩戴时间，也可越来越多地用于 日常一次性用品包括亲水性聚甲基丙烯酸羟乙酯、疏水性有机硅大分子单体 相和剩余的水孔，同时获得高透明度、撕裂亲和力和氧气 变速箱。这种纳米结构自然具有非常高的孔表面积与体积比，这是我们 将通过设计的表面修饰来控制药物释放。传递带电的药物分子， 在聚合物-水孔界面上引入相反电荷的配体基团将增强 分子在界面上的分配和滞留。因此，由于格外大的表面积 纳米结构域，有效和精确地控制其从DDCL中的释放动力学。Lynthera的技术使 一种直接结合长链脂肪酸、胺或季胺的边界表面修饰方案 将铵盐涂在亲水性聚甲基丙烯酸羟乙酯或有机硅聚合物表面以容纳 近80%的离子药物在一个镜片中。滞留发生在形成于 大面积的聚合物-孔道界面。我们的改装方案将大幅提高电荷密度 镜片-孔界面--尤其是硅胶水凝胶镜片--从而提高了精度、持续时间和 酮替芬给药的综合效果，以及由于硅胶而延长舒适的佩戴时间 水凝胶镜片的氧气透过率更高。具体目标1是开发更好的(持续时间更长，更高 更精确，更舒适)酮替芬洗脱DDCL，在日常一次性隐形眼镜市场竞争。 具体目标2是开发一种可持续和高精度的奥洛他定每日一次性递送 通过在聚合物孔边界表面设计电荷配体来设计接触镜，克服了 控制这种广受欢迎的非处方药过敏药物的输送。

PROJECT SUMMARY Among the estimated 165 million worldwide contact lens wearers many suffer from allergies but face a challenge as the application of eye drops is generally incompatible with lens wearing. It has been estimated one third contact lens wearers experience itchy eyes; and a majority of these are frustrated that allergy interferes with their normal wear and often they rely on allergy eye drops to manage their symptoms. The first approval of a medicated contact lens that addresses this need occurred only recently (2021) when Johnson & Johnson's Acuvue Theravision with ketotifen drug eluting daily disposable hydrogel lens received marketing authorization in Japan. We propose to develop a next-generation drug delivery contact lens (DDCL) platform for allergy drugs using boundary charge modifiers to extend and control drug release. The work will build on our previous accomplishments in the field—enabling the use of both the most efficacious drugs and the most breathable lenses. The new Johnson & Johnson product requires compromises in both areas to accomplish just a few hours duration of release. Many commercial contact lenses intended for both for extended wear and increasingly for daily disposable wear consist of hydrophilic poly (2-hydroxyethyl methacrylate), hydrophobic silicone macromer phase and remainder aqueous pores to simultaneously achieve high transparency, tear affinity, and oxygen transmission. This nanodomain structure naturally has a very high pore surface area to volume ratio, which we will utilize to control drug release with designed surface modifications. For delivering a charged drug molecule, the incorporation of an oppositely charged ligand group at the polymer-aqueous pore interfaces will enhance the molecule's partition and retention at the interfaces. Thus, due to the exceptionally large surface areas of the nanodomains, effectively and precisely control its release kinetics from a DDCL. Lynthera's technology enables a boundary surface modification scheme to directly incorporate long-chain fatty acids, amines, or quaternary ammonium salts onto either hydrophilic poly (2-hydroxyethyl methacrylate) or silicone polymer surfaces to house nearly 80% of ionic drugs in a lens. The retention occurs within the charged boundary double layers formed at the large area of polymer-pore interfaces. Our modification scheme will substantially raise the charge density at the lens-pore interfaces – especially for silicone hydrogel lenses – thereby raising the precision, duration, and resultant efficacy of ketotifen drug delivery, as well as prolonging comfortable wear time due to the silicone hydrogel lenses' higher oxygen transmission. Specific Aim 1 is to develop a better (longer duration, higher precision, and more comfort) Ketotifen eluting DDCL to compete in the daily disposable contact lens market. Specific Aim 2 is to develop a sustainable and high-precision delivery of Olopatadine from a daily disposable contact lens by design of charge ligands at the polymer pore boundary surfaces that overcome the challenge of controlling delivery of this popular OTC allergy drug.