Drug delivery platform for ocular allergy therapy

用于眼部过敏治疗的药物输送平台

• 批准号: 10484648
• 负责人: Arthur Yang
• 金额: $ 30万
• 依托单位: LYNTHERA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484648
• 关键词: Address; Affinity; Amines; Ammonium; Anions; Anti-Allergic Agents; Area; Authorization documentation; Canada; Cell Survival; Charge; Clinical Research; Complex; Contact Lenses; Data; Development; Devices; Dose; Dropout; Drug Controls; Drug Delivery Systems; Drug Hypersensitivity; Drug Targeting; Drug usage; Dry Eye Syndromes; Dryness; Electrostatics; Eye; Eyedrops; Face; Fatty Acids; Film; Fumarates; Future; Homeostasis; Hour; Human; Hydrogels; Hydrophobicity; Hypersensitivity; Injections; Japan; Kinetics; Legal patent; Ligands; Marketing; Measures; Methacrylates; Modification; Modulus; Mus; New Zealand; Non-Prescription Drugs; Optics; Organ; Oryctolagus cuniculus; Oxygen; Permeability; Pharmaceutical Preparations; Phase; Physiological; Polymers; Pre-Clinical Model; Property; Publications; Reporting; Research; Role; Salts; Scheme; Silicones; Solubility; Structure; Surface; Symptoms; System; Technology; Time; Toxic effect; Vision; Visual; Water; Work; acute toxicity; aqueous; controlled release; density; design; dosage; efficacy study; experience; hydrophilicity; innovation; interfacial; invention; irritation; lens; long chain fatty acid; manufacturing process; methacrylic acid; nanocomposite; next generation; pharmacokinetics and pharmacodynamics; prototype; systemic toxicity; transmission process

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.

项目概要 全球估计有 1.65 亿隐形眼镜佩戴者，其中许多人患有过敏，但面临着挑战 因为眼药水的使用通常与镜片的佩戴不相容。估计有三分之一 隐形眼镜佩戴者会感到眼睛发痒；其中大多数人对过敏干扰他们的生活感到沮丧 正常佩戴，他们通常依靠过敏眼药水来控制症状。第一次批准 满足这一需求的药用隐形眼镜直到最近（2021 年）才出现，当时强生公司的 Acuvue Theravision 含酮替芬药物洗脱日抛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输送隐形眼镜（DDCL）平台 使用边界电荷调节剂来延长和控制药物释放。这项工作将建立在我们之前的基础上 该领域的成就——使得能够使用最有效的药物和最透气的材料 镜头。强生公司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 释放的持续时间。许多商业隐形眼镜旨在长期佩戴，并且越来越多地用于 日常一次性服装由亲水性聚（甲基丙烯酸 2-羟乙酯）、疏水性有机硅大分子单体组成 相和剩余水孔同时实现高透明度、亲泪性和氧气 传播。这种纳米域结构自然具有非常高的孔表面积与体积比，我们 将用于通过设计的表面修饰来控制药物释放。为了递送带电药物分子， 在聚合物-水孔界面处引入带相反电荷的配体基团将增强 分子在界面上的分配和保留。因此，由于表面积异常大 纳米域，有效且精确地控制其从 DDCL 中的释放动力学。 Lynthera 的技术使 直接掺入长链脂肪酸、胺或季铵盐的界面改性方案 将铵盐附着到亲水性聚（甲基丙烯酸 2-羟乙酯）或有机硅聚合物表面以容纳 近80%的离子药物在晶状体中。保留发生在形成于以下位置的带电边界双层内： 大面积的聚合物-孔界面。我们的修改方案将大大提高电荷密度 镜片-孔隙界面——尤其是硅水凝胶镜片——从而提高了精度、持续时间和 酮替芬药物输送的综合功效，以及由于硅胶而延长舒适佩戴时间 水凝胶镜片具有更高的氧气透过率。具体目标 1 是开发更好的（更长持续时间、更高 精度更高、更舒适）酮替芬洗脱 DDCL，以参与日抛隐形眼镜市场的竞争。 具体目标 2 是开发一种从日常一次性用品中可持续、高精度输送奥洛他定的方法 通过在聚合物孔边界表面设计电荷配体来克服隐形眼镜的挑战 控制这种流行的非处方抗过敏药物的输送。