Drug delivery platform for ocular allergy therapy

项目摘要 在全球约1.65亿隐形透镜佩戴者中，许多人患有过敏症，但面临着一个挑战， 因为滴眼液的应用通常与透镜的佩戴不相容。据估计， 隐形透镜佩戴者经历眼睛发痒;并且这些人中的大多数对过敏干扰他们的视力而感到沮丧。 正常佩戴，他们经常依靠过敏眼药水来控制他们的症状。第一次批准A 满足这一需求的含药接触透镜最近（2021年）才出现，当时约翰逊和约翰逊的 Acuvue Theravision与酮替芬药物洗脱日抛型水凝胶透镜获得上市许可 在日本我们建议开发下一代药物递送接触透镜（DDCL）平台，用于过敏药物 使用边界电荷改性剂来延长和控制药物释放。这项工作将建立在我们以前的 在该领域的成就-使最有效的药物和最透气的使用 眼镜.新的约翰逊和约翰逊产品需要在这两个方面的妥协，以完成短短几个小时 释放的时间。许多商业隐形眼镜旨在用于长期佩戴和越来越多地用于 由亲水性聚（甲基丙烯酸2-羟乙酯）、疏水性硅氧烷大分子单体 相和剩余的水性孔，以同时实现高透明度、泪液亲和力和氧 传输这种纳米畴结构自然具有非常高的孔表面积与体积比， 将利用设计的表面改性来控制药物释放。为了输送带电药物分子， 在聚合物-水孔界面处引入带相反电荷的配体基团将增强 分子在界面的分配和滞留。因此，由于所述膜的特别大的表面积， 纳米结构域，有效和精确地控制其从DDCL的释放动力学。Lynthera的技术使 边界表面改性方案，以直接掺入长链脂肪酸、胺或季铵盐， 将铵盐涂覆到亲水性聚（甲基丙烯酸2-羟乙酯）或硅氧烷聚合物表面上， 透镜中近80%的离子药物。保留发生在形成的带电边界双层内， 大面积的聚合物-孔界面。我们的改进方案将大大提高电荷密度， 透镜-孔界面-特别是对于硅酮水凝胶透镜-从而提高了精确度、持续时间， 酮替芬药物递送的最终功效，以及由于硅酮而延长的舒适佩戴时间 水凝胶镜片具有更高的氧气透过率。具体目标1是制定一个更好的（更长的时间，更高的 更精确、更舒适）酮替芬洗脱DDCL在日抛型接触透镜市场竞争。 具体目标2是开发一种可持续的和高精度的奥洛他定输送方法， 接触透镜，其通过在聚合物孔边界表面处设计电荷配体来克服以下挑战： 控制这种流行的非处方抗过敏药的输送。

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.