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: 10256580
• 负责人: Roman Domszy
• 金额: $ 30万
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10256580
• 关键词: Adherence; Adhesions; Adsorption; Adult; Affect; Age; American; Animals; Autoimmune Responses; Biological Availability; Biological Markers; Cations; Cell physiology; Cells; Centers for Disease Control and Prevention (U.S.); Charge; Clinical Trials; Conjunctival Epithelium; Contact Lenses; Cornea; Cyclosporine; Devices; Diagnosis; Diffusion; Disease; Dosage Forms; Dose; Drug Delivery Systems; Dry Eye Syndromes; Dryness; Effectiveness; Electrostatics; Emulsions; Engineering; Environment; Etiology; Eye; Eyedrops; Family suidae; Film; Formulation; Functional disorder; Generations; Graft Rejection; Homeostasis; Hour; Human; Hydrogels; Hydrophilic Contact Lenses; Hypoxia; Immune response; Immunomodulators; Immunosuppressive Agents; In Vitro; Individual; Inflammation; Inflammatory; Institutes; Keratoplasty; Kinetics; Measures; Modeling; Nanotechnology; Oleic Acids; Organ Model; Outcome; Oxygen; Patients; Penetrating Keratoplasty; Penetration; Permeability; Pharmaceutical Preparations; Phase; Physiological; Play; Polyethylene Glycols; Population; Prevalence; Procedures; Prophylactic treatment; Quality of life; Role; Services; Severities; Silicones; Solubility; Sphingolipids; Surface; Symptoms; T-Lymphocyte; Technology; Therapeutic; Therapeutic Agents; Thinness; Time; Tissues; Toxic effect; Translating; Treatment Efficacy; United States; Vision; Woman; Work; aged; alpha Tocopherol; anterior chamber; aqueous; arm; base; biomaterial compatibility; cell mediated immune response; conjunctiva; corneal epithelium; cytotoxicity; dosage; drug efficacy; effective therapy; improved; irritation; lens; lipophilicity; nanocarrier; nanoemulsion; novel; novel therapeutics; ocular surface; persistent symptom; prototype; residence; side effect; success; surfactant; 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. The project team proposes to incorporate cyclosporine into a contact lens to better deliver the active ingredient and potentially with fewer side effects as the dosing is better controlled. It is known that drug delivery from a contact lens can result in several times higher bioavailability than eye drops due to the direct transfer of a drug to cornea across a thin tear layer. Using our dual layer contact lens platform and charged boundary layer technology we will resolve the deficiencies of current therapy by (1) Delivering cyclosporine at low concentration consistently for 8 hours/day using a drug eluting contact lens to allow a precise accumulation of cyclosporine on corneal surface, (2) Delivering cyclosporine loaded cationic nanocarriers from a novel drug eluting contact lens to improve the nanocarrier adhesion to cornea and conjunctiva surface and enhance cyclosporine penetration into the anterior chamber, (3) Conducting in vitro cell-based cytotoxicity studies of the nanocarriers and by means of an ex vivo porcine eye model measure cyclosporine corneal penetration efficacy of the drug eluting contact lens devices.

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。项目组建议 将环孢素添加到隐形眼镜中，以更好地传递活性成分，并可能减少副作用 效果，因为剂量控制得更好。众所周知，从隐形眼镜递送药物会导致几个 由于药物通过一层薄薄的泪层直接转移到角膜，其生物利用度比滴眼液高出两倍。 使用我们的双层隐形眼镜平台和带电边界层技术，我们将解决这些不足 目前的治疗方法是：(1)每天持续使用一种药物以低浓度给药8小时 洗脱隐形眼镜以使环孢素在角膜表面精确积累，(2)输送 环孢素负载新型药物洗脱隐形眼镜阳离子纳米载体的研究 黏附于角膜和结膜表面，促进环孢素进入前房， (3)进行基于细胞的纳米载体的体外细胞毒性研究，并通过体外猪 眼部模型测量环孢素A药物洗脱隐形眼镜装置的角膜穿透效果。