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.

项目总结 1600万美国人被诊断出患有干眼症，可能还有更多的人患有这一疾病。 患病率在女性中更高，随着年龄的增长而增加，现在在18-34岁的人群中也很明显 好几年了。它的特征是泪膜动态平衡的丧失，并可能伴随着持续性 刺激或灼伤的症状，如果不治疗，可能会对角膜和结膜造成炎症损害。 目前通过减少眼部炎症而起作用的眼药水疗法有几种 可能会让患者感到沮丧的缺陷。免疫调节剂环孢素通常在 这些滴眼液使用各种递送载体，包括阴离子乳剂、阳离子纳米乳剂或 纳米胶束溶液。然而，由于以下原因，车辆延长角膜停留时间的影响仍然有限 自然的眼睛防御机制。这被认为是常见的干眼症的原因之一 在临床试验中，用这种眼药水治疗并不会有更好或更快的疗效。在这个第二阶段的项目中，我们 建议继续成功地开发设计用于管理干燥的药物递送隐形眼镜(DDCL) 通过加入环孢素A(CsA)来更好地传递活性成分，并减少副作用 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 摄取和滞留，由于HA自身的润滑和再生能力，有可能更快地缓解症状 作为一种自然存在于体内的物质的特性。随着第一阶段的主要目标基本完成， 第二阶段将重点优化使用CSA和HA的DDCL，使用来自商业 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。该产品 然后可以很容易地集成到现有的隐形眼镜生产工艺中，用于以下临床试验 这个项目。成功完成第二阶段研究战略将包括活体研究的积极结果 以及用于人类人群DDCL临床研究的IND应用。对于商业化战略， 我们与一家全球隐形眼镜公司达成了制造和供应DDCL的协议，并 与此合作伙伴协商选定地区的许可协议。投资和未来的版税 合作伙伴将允许我们在未来为其他市场自主开发DDCL。