Sustained delivery technology for Cyclosporine A in the treatment of autoimmune response

环孢素 A 持续递送技术治疗自身免疫反应

• 批准号: 10698850
• 负责人: Roman Domszy
• 金额: $ 79.5万
• 依托单位: LYNTHERA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698850
• 关键词: Adsorption; Adult; Affect; Age; Agreement; American; Anti-Inflammatory Agents; Antioxidants; Artificial Tears; Autoimmune Responses; Biological Availability; Cell Density; Characteristics; Chemistry; Clinical Research; Clinical Trials; Contact Lenses; Cornea; Cyclic GMP; Cyclosporine; Development; Diagnosis; Disease; Dose; Drainage procedure; Drops; Drug Delivery Systems; Drug Kinetics; Dry Eye Syndromes; Dryness; Emulsions; Epithelium; Etiology; Eye; Eyedrops; Film; Formulation; Friction; Frustration; Future; Glycocalyx; Glycoproteins; Goals; Goblet Cells; Growth; Homeostasis; Human; Hyaluronic Acid; Hydrogels; Hydrophobicity; Hypoxia; Immune response; Immunomodulators; In Vitro; Industrialization; Inflammation; Inflammatory; Investigational Drugs; Investigational New Drug Application; Investments; Licensing; Life; Lubrication; Manufacturer; Marketing; Mediation; Methods; Modeling; Mucins; Natural Substance; New Zealand; Oryctolagus cuniculus; Oxygen; Patients; Permeability; Persons; Pharmaceutical Preparations; Phase; Play; Population; Prevalence; Process; Production; Property; Protocols documentation; Reporting; Research; Rights; Role; Services; Silicones; Small Business Innovation Research Grant; Solubility; Source; Surface; Symptoms; T-Lymphocyte; Technology; Therapeutic; Thinness; Time; Woman; Work; aged; aqueous; arm; bulbar conjunctiva; cell mediated immune response; commercialization; conjunctiva; delivery vehicle; design; dosage; drug development; eye dryness; hydrophilicity; immunomodulatory therapies; improved; in vivo; innovation; irritation; lens; lipophilicity; manufacture; meter; migration; nano; nanoemulsion; nanoformulation; novel; ocular surface disease; persistent symptom; pre-Investigational New Drug meeting; product development; prototype; reduce symptoms; regenerative; residence; response; restoration; side effect; therapeutic target; tv watching; uptake

PROJECT SUMMARY Sixteen million Americans are diagnosed with dry eye disease, with likely many more suffering from this issue. Prevalence is higher among women, increases with age, and is now also notable among those aged 18–34 years. It is characterized by a loss of homeostasis of the tear film and may be accompanied by persistent symptoms of irritation or burning that can cause inflammatory damage to the cornea and conjunctiva if untreated. Current eye-drop treatments that work by reducing the inflammation on the ocular service have several deficiencies that can be frustrating for patients. The immunomodulator, cyclosporine, is commonly prescribed in these eye drops using a variety of delivery vehicles including anionic emulsions, cationic nanoemulsions, or nanomicellar solutions. However, the impact of the vehicle to prolong corneal residence is still limited due to natural ocular defensive mechanisms. This is believed to be one reason that the common dry eye disease treatment by such eye drops do not have better or faster efficacy in clinical trials. In this Phase II project, we propose continuing the successful development of a drug delivery contact lens (DDCL) designed to manage dry eye by incorporating cyclosporine A (CsA) to better deliver the active ingredient with fewer side effects due to better control of dosing. An important discovery in Phase I was the use of hyaluronic acid (HA) improving CsA uptake and retention, with the potential for faster relief of symptoms due to HA's own lubricating and regenerative properties as a naturally occurring substance in the body. With the key aims of Phase I substantially completed, Phase II will focus on optimizing the DDCL with CsA and HA using active ingredients sourced from commercial manufacturers, and lenses with FDA 510(k) clearance for which we have rights to commercial use. The product can then be easily integrated into an existing contact lens production process for use in clinical trials following the project. Successful completion of the Phase II research strategy will include positive results by in vivo study and an IND application for clinical study of the DDCL in a human population. For the commercialization strategy, we have agreement with a global contact lens company to manufacture and supply the DDCL, and are negotiating a licensing agreement with this partner for selected regions. Investment and future royalties from the partner will allow our independent development of the DDCL for other markets in the future.

项目摘要 一千六百万美国人被诊断患有干眼病，可能还有更多的人患有这种疾病。 妇女中的流行率较高，随着年龄的增长而增加，现在在18-34岁的人中也很明显 年其特征在于泪膜的内稳态丧失，并可伴有持续的 如果不治疗，可能导致角膜和结膜炎性损伤的刺激或烧灼症状。 目前通过减少眼部炎症而起作用的滴眼液治疗有几种 这些缺陷可能会让患者感到沮丧。免疫调节剂环孢霉素通常是处方药， 这些滴眼剂使用多种递送载体，包括阴离子乳液、阳离子纳米乳液或 纳米胶束溶液。然而，车辆延长角膜驻留的影响仍然有限， 天然的眼部防御机制这被认为是常见的干眼病 在临床试验中，通过这种滴眼剂的治疗没有更好或更快的功效。在第二阶段，我们 建议继续成功开发药物递送接触透镜（DDCL）， 通过掺入环孢菌素A（CsA），以更好地递送活性成分，同时减少由于 更好地控制剂量。第一阶段的一个重要发现是使用透明质酸（HA）改善CsA 吸收和保留，由于HA自身的润滑和再生作用， 作为一种天然存在于体内的物质。随着第一阶段的主要目标基本完成， 第二阶段将集中于使用来自商业的活性成分优化CsA和HA的DDCL 制造商和获得FDA 510（k）许可的镜片，我们有权将其用于商业用途。产品 然后可以容易地集成到现有的接触透镜生产过程中 该项目成功完成II期研究策略将包括体内研究的积极结果 以及在人群中进行DDCL临床研究的IND申请。对于商业化战略， 我们与一家全球性的接触透镜公司达成协议，生产和供应DDCL， 与该合作伙伴就选定区域的许可协议进行谈判。投资和未来的特许权使用费 合作伙伴将允许我们在未来为其他市场独立开发DDCL。